Mona-Elisabeth Rootwelt-Revheim

• Motamedi, Niloofaralsadat; Singh, Shashi Bhushan; Ismoilov, Miraziz; Niazi, Saira K.; Shrestha, Bimash B. & Ahmed, Malia [Show all 11 contributors for this article] (2026). Application of [¹⁸F]NaF and [¹⁸F]FDG PET/CT to Assess Molecular Calcification and Glucose Metabolism in Thyroid Cartilage. Cartilage. ISSN 1947-6035. doi: 10.1177/19476035261467882. Full text in Research Archive
• Kata, Rithvik; Patel, Darshil; Gandhi, Om H.; Sankisa, Divya; Schwartz, Devi K. & Patil, Shiv [Show all 12 contributors for this article] (2026). Spinal cord FDG PET uptake in healthy adults: an AI-driven segmentation study. European spine journal. ISSN 0940-6719. doi: 10.1007/s00586-026-10049-5. Full text in Research Archive Show summary

  Purpose 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized Tomography (CT) is an important imaging modality in oncology, but its use in spinal cord assessment is limited due to a lack of baseline metabolic reference values. Regional spinal cord FDG uptake, especially in healthy populations, remains poorly defined, limiting accurate delineation between physiological and pathological uptake. The study aimed to quantify regional FDG uptake in the cervical, thoracic, and lumbar spinal cord in healthy adults, and evaluate associations between FDG uptake and demographic factors, including age, sex, body mass index (BMI), and inflammatory/metabolic biomarkers. A secondary aim was to apply artificial intelligence (AI)-driven segmentation to facilitate standardized region-of-interest extraction across spinal cord levels. Methods This was a retrospective, cross-sectional observational study conducted using data from the CAMONA clinical trial at Odense University Hospital, Denmark. 76 healthy adult participants (mean age 44.66 ± 14.04 years; 53.9% male) were selected from a total of 139 subjects in the CAMONA trial. All participants were free from chronic medical conditions. Primary outcomes include mean standardized uptake values (SUVmean) of FDG in the cervical, thoracic, and lumbar spinal cord regions. Secondary outcomes include correlations of SUVmean with age, sex, BMI, HbA1c, and inflammatory biomarkers (CRP, WBC, homocysteine, fibrinogen). Participants underwent FDG PET/CT imaging 180 min post-injection of 4.0 MBq/kg FDG. Using TotalSegmentator, an AI-driven segmentation tool, the spinal cord was delineated into cervical, thoracic, and lumbar volumes of interest (VOIs). Regional SUVmeans were calculated and analyzed. Statistical tests included one-way ANOVA with Tukey’s post-hoc, Spearman/Pearson correlations and t-tests to assess associations with age, sex, BMI, and inflammatory/metabolic biomarkers. Results FDG uptake was highest in the cervical spinal cord (SUVbw 1.36 ± 0.23), followed by the lumbar (0.85 ± 0.18) and thoracic (0.76 ± 0.17) regions (p < 0.001); this regional ordering was preserved after lean-body-mass-normalized SUV (SUL) recomputation. No significant associations were found with age or sex. BMI correlated positively with SUVbw across all regions (ρ = 0.34–0.47, all p ≤ 0.003); under SUL, the cervical and thoracic associations attenuated to non-significance (cervical ρ = +0.13, p = 0.255; thoracic ρ = +0.17, p = 0.151), whereas a residual lumbar association persisted (ρ = +0.32, 95% CI + 0.09 to + 0.52, p = 0.004). A nominal association between HbA1c and cervical uptake (ρ = 0.24, p = 0.040) did not survive Bonferroni correction for multiple comparisons (α = 0.0033) and is reported as exploratory. Inflammatory markers showed no significant correlation in any spinal cord region. Conclusion FDG PET/CT reveals consistent regional variation in spinal cord metabolic activity, with highest uptake in the cervical region. Normative uptake was stable across age and sex but showed a positive association with BMI when SUV was normalized to total body weight that was largely abolished after lean-body-mass normalization (SUL) in the cervical and thoracic regions but persisted in the lumbar region (lumbar SUL ρ = +0.32, 95% CI + 0.09 to + 0.52, p = 0.004). These findings offer foundational data for clinical interpretation and differentiation between physiology and pathology of spinal FDG PET/CT uptake and demonstrate the feasibility of AI-driven segmentation for standardized region-of-interest extraction in spinal imaging analysis.

• Gandhi, Om H.; Gujral, Jaskeerat; Amanullah, Amir A.; Patil, Shiv; Subtirelu, Robert C. & Teichner, Eric M. [Show all 10 contributors for this article] (2026). Characterization of regional brain metabolic changes in metastatic melanoma using¹⁸F-FDG PET/CT imaging: A casereport. Hellenic Journal of Nuclear Medicine (HJNM). 29(1), p. 34–38. doi: 10.1967/s002449912944. Full text in Research Archive
• Singh, Shashi B.; Gandhi, Om H.; Haghshenas, Cameron; Shrestha, Bimash B.; Ahmed, Malia & Gujral, Jaskeerat [Show all 19 contributors for this article] (2026). Metabolic changes in reticuloendothelial system following Tisagenlecleucel chimeric antigen receptor T cell (CAR-T) therapy using¹⁸F-FDG PET/CT. Hellenic Journal of Nuclear Medicine (HJNM). 29(1), p. 2–9. doi: 10.1967/s002449912940. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Alavi, Abass; Andalib, Sasan; Castellani, Rudolph J.; Costa, Tommaso & Girolamo, Giovanni de [Show all 14 contributors for this article] (2026). Serious side effects of Alzheimer’s immunotherapy demand scrutiny. Ageing Research Reviews. ISSN 1568-1637. 119. doi: 10.1016/j.arr.2026.103151. Full text in Research Archive
• Lysvik, Elisabeth Kirkeby; Tulipan, Andreas Julius; Haakensen, Vilde Drageset; Rootwelt-Revheim, Mona-Elisabeth; Emblem, Kyrre Eeg & Hjørnevik, Trine (2026). Quantitative [18F]PSMA-1007 PET in Treatment Response Monitoring of Brain Metastases from Non-small Cell Lung Cancer. Molecular Imaging and Biology. ISSN 1536-1632. doi: 10.1007/s11307-026-02104-w. Full text in Research Archive Show summary

  Purpose Prostate-specific membrane antigen (PSMA) is expressed in several solid tumours, including brain metastases (BMs) from lung cancer. We investigated quantitative [18F]PSMA-1007 uptake and treatment response in BMs of patients with non-small cell lung cancer (NSCLC). Procedures Eleven patients with BM of NSCLC underwent 95-min dual-time-point dynamic [18F]PSMA-1007 PET/CT and a whole-body static scan before and after stereotactic radiosurgery (SRS) with a median dose of 20 Gy (range: 8–25 Gy) given in a median of 1 fraction (range: 1–3). Seven patients completed both exams. Image-derived input functions were extracted from the internal carotid arteries, and pharmacokinetic analysis using Patlak modelling yielded the influx constant (Ki). Standardised uptake value (SUV), biological tumour volume (BTV) and tumour heterogeneity using the coefficient of variance (CoV) were assessed. Results [18F]PSMA-1007 PET showed uptake in the first exam in BMs and primary lung tumour in all patients. Significant inter-patient and intra-lesion heterogeneity in tracer uptake was observed in BMs with median Ki of 0.005 ml/ccm/min (range: 0.003–0.018 ml/ccm/min), SUVpeak of 4.2 g/ml (range: 0.4–34.4 g/ml), CoV of 0.36 (range 0.06–0.85) and BTV of 2.35 ml (range 0.03–22.29 ml). After SRS, reductions in Ki (37%), SUVpeak (50%), CoV (24%) and BTV (71%) were noted. Median SUVpeak in the lungs were 6.1 g/ml (range: 3.2–13.6 g/ml) at the initial exam and 6.3 g/ml (range: 3.8–11.8 g/ml) at the second exam. Conclusion [18F]PSMA-1007 PET is a promising diagnostic tool for BMs from NSCLC. The uptake and heterogeneity, along with the marked reduction post-therapy, highlights its potential for monitoring treatment response.

• Butt, Baddar Pervaiz; Sørbye, Halfdan; Ladekarl, Morten; Stokmo, Henning Langen; Lothe, Inger Marie Bowitz & Fawad, Haris [Show all 12 contributors for this article] (2026). Efficacy of FOLFIRINOX in digestive neuroendocrine carcinoma. Journal of Neuroendocrinology (JNE). ISSN 0953-8194. 38(4). doi: 10.1111/jne.70168. Full text in Research Archive
• Johannessen, Karl Arne; Royall, Paul G.; Mjøs, Anders; Saga, Thor Audun & Rootwelt-Revheim, Mona-Elisabeth (2026). Enhancing Access to Cancer Diagnostics with Drone Delivery of PET Isotopes: The Significance of Weather and Clinical Workflows. Drones. 10(3). doi: 10.3390/drones10030202. Full text in Research Archive
• Holm, Maia Blomhoff; Dorg, Linda Trobe; Rootwelt-Revheim, Mona-Elisabeth; Labori, Knut Jørgen & Verbeke, Caroline Sophie (2026). Expression of glycolytic markers in cancer and stromal cells of treatment-naïve and neoadjuvantly treated pancreatic ductal adenocarcinoma. Virchows Archiv. ISSN 0945-6317. doi: 10.1007/s00428-026-04478-2. Full text in Research Archive
• Gujral, Jaskeerat; Ghandi, Om H; Amanullah, Amir A; Singh, Shashi B; Ayubcha, Cyrus & Werner, Thomas J [Show all 8 contributors for this article] (2025). Somatostatin receptor PET-guided treatment and artificial intelligence applications in meningioma: a comprehensive review. The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI). 15(6), p. 223–235. doi: 10.62347/lyat6783. Full text in Research Archive
• Gandhi, Om H; Lee, Andrew E.; Gujra, Jaskeerat; Ismoilov, Miraziz; Singh, Shashi B & Ghonim, Mohanad [Show all 17 contributors for this article] (2025). Maxillary sinus inflammation assessment using FDG-PET/CT in head and neck cancer patients with photon, proton, and combined radiation therapy. The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI). 15(3), p. 97–104. doi: 10.62347/gldl6616. Full text in Research Archive
• Berner, Kjetil; Hernes, Eivor; Kvassheim, Monika; Rootwelt-Revheim, Mona-Elisabeth; Bastiansen, Julie Inderberg & Selboe, Silje [Show all 13 contributors for this article] (2025). First-in-Human Phase 0 Study of AB001, a Prostate-Specific Membrane Antigen–Targeted 212Pb Radioligand, in Patients with Metastatic Castration-Resistant Prostate Cancer. Journal of Nuclear Medicine. ISSN 0161-5505. 66(5), p. 732–738. doi: 10.2967/jnumed.124.269299. Full text in Research Archive Show summary

  AB001, a prostate-specific membrane antigen (PSMA)–targeted small molecule labeled with the in vivo–generating α-emitter 212Pb, was investigated in a phase 0 trial in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary objective was to explore the feasibility of γ-camera imaging to assess biodistribution and uptake in metastatic lesions. Methods: Three patients with progressive mCRPC and Eastern Cooperative Oncology Group performance status 1 were included, having prostate-specific antigen levels of 0.44, 0.75, and 15 µg/L. All had at least 3 PSMA-expressing metastatic lesions, with an SUVmax range of 10.1–77.4 on PSMA PET. Each patient received a microdose of 9.4 ± 0.3 MBq of AB001 intravenously. Planar γ-camera and SPECT/CT imaging was scheduled 1–3 h and 16–24 h after administration. Whole-body clearance was assessed with NaI probe measurements. Activity of 212Pb in whole blood and plasma was measured to investigate clearance from blood and in vivo stability of the ligand. Safety, tolerability, and efficacy biomarkers (prostate-specific antigen, alkaline phosphatase) were followed for 28 d. Results: AB001 uptake in the lesion with the highest PSMA expression, a retrocaval lymph node metastasis with a short-axis diameter of 11 mm, was visualized on SPECT. Uptake of AB001 was not clearly demonstrated for other metastatic lesions, possibly because of the lower PSMA expression of these metastases on PSMA PET, combined with the administered AB001 microdose and imaging system limitations. Kidney, urinary bladder with contents, and liver uptake of AB001 were clearly distinguishable from adjacent tissue, and the blood pool content was seen. Salivary glands were not visualized. Blood analyses indicated stability of AB001 after injection, and whole-body probe measurements demonstrated an effective half-life of 8 h. There were no complications related to injection of AB001 or adverse reactions during follow-up. As expected for a phase 0 study, there was no indication of therapeutic effects as assessed by prostate-specific antigen and alkaline phosphatase. Conclusion: The 212Pb-based radioligand AB001 was safely administered to mCRPC patients. γ-camera imaging of AB001 was feasible, even at a microdose, and demonstrated metastatic targeting, albeit for only 1 lesion. The promising biodistribution and clearance encourage further clinical investigation

• Subtirelu, Robert C.; Teichner, Eric M.; Writer, Milo; Bryan, Kevin; Patil, Shiv & Khan, Talha [Show all 13 contributors for this article] (2025). Optimizing Stereotactic Intracranial Neoplasm Treatment: A Systematic Review of PET Integration with Gamma Knife Radiosurgery. Diseases. 13(7). doi: 10.3390/diseases13070215. Full text in Research Archive
• Teichner, Eric M.; Subtirelu, Robert C.; Crutchfield, Connor R.; Parikh, Chitra; Ashok, Arjun & Talasila, Sahithi [Show all 14 contributors for this article] (2025). The advancement and utility of multimodal imaging in the diagnosis of degenerative disc disease. Frontiers in Radiology. 5. doi: 10.3389/fradi.2025.1298054. Full text in Research Archive Show summary

  Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using 18F- fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT grading of the disease. The novel hybrid imaging modality PET/MRI provides new opportunities and are briefly discussed. The complex pathophysiology of DDD is dissected to highlight the role of genetic predisposition and lifestyle factors such as smoking and obesity. These etiological factors significantly impact the lumbosacral region, manifesting in chronic low back pain (LBP) and potential nerve compression. Traditional grading systems, like the Pfirrmann classification for MRI, are evaluated for their limitations in capturing the full spectrum of DDD. The potential to identify early disease processes and predict patient outcomes by the use of artificial intelligence (AI) is also briefly mentioned. Overall, the manuscript aims to spotlight advancements in imaging technologies for DDD, emphasizing their implications in refining both diagnosis and treatment strategies. The role of ongoing and future research is emphasized to validate these emerging techniques and overcome current limitations for more effective early detection and treatment.

• Singh, Shashi B.; Gandhi, Om H.; Shrestha, Bimash B.; Glennan, Patrick; Bahadur, Anuradha Rosario & Motamedi, Niloofaralsadat [Show all 12 contributors for this article] (2025). [18F]NaF PET/CT Imaging of Iliac Bones to Assess Bone Turnover. Molecular Imaging and Biology. ISSN 1536-1632. 27(3), p. 295–304. doi: 10.1007/s11307-025-02003-6. Full text in Research Archive
• Nørgaard, Jakob Nordberg; Abildgaard, Niels; Lysén, Anna Karin Christina; Tsykunova, Galina; Vangsted, Annette Juul & João, Cristina [Show all 12 contributors for this article] (2025). Progression-Free and Overall Survival After KRd Consolidation in FDG PET/CT Positive Patients After ASCT: A Phase II Study (CONPET). Clinical Lymphoma, Myeloma & Leukemia. ISSN 2152-2650. 26(3), p. e335–e343. doi: 10.1016/j.clml.2025.10.020. Full text in Research Archive
• Ahmed, Malia; Gandhi, Om H.; Singh, Shashi B.; Gujral, Jaskeerat; Park, Peter K. & Shrestha, Bimash B. [Show all 12 contributors for this article] (2025). Application of [18F]-fluorodeoxyglucose PET/computed tomography to measure volume and metabolic activity of arm muscles. Nuclear medicine communications. ISSN 0143-3636. 46(11), p. 1090–1096. doi: 10.1097/MNM.0000000000002038. Full text in Research Archive Show summary

  Objective This study aimed to introduce a computed tomography (CT)-based tissue segmentation technique to quantify the volume and metabolic activity of the arm muscles using [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT. Methods Eighty-seven subjects from the CAMONA study were included. A semiautomated three-dimensional segmentation algorithm was used to highlight the muscle. The [18F]FDG uptake was measured as mean standardized uptake value (SUV) normalized to body weight (SUVBW) and to lean body mass (SUVLBM). To acquire normalized volume, arm muscle volume, humerus volume, and humerus length were used. The average SUVmean was calculated from independently measured volumes (cm3) of the left and right muscle groups. The obtained SUVBW, SUVLBM, and normalized volume were used to compare the right and left arms. Results Between right and left arm muscles, there was significantly higher uptake of SUVBW and SUVLBM in the right arm compared with the left (P < 0.001). Between males and females, there was a significantly higher SUVBW in the right arm for females (P = 0.03) and significantly higher normalized volume on both right and left arms for males (right, P < 0.001; left, P < 0.001). Conclusion [18F]FDG PET/CT using CT-based segmentation enables analysis of total arm muscle metabolic activity and volume. This methodology demonstrated significant differences in mean SUVBW and SUVLBM between the left and right arms, with consistently higher uptake in the right arm. In addition, females exhibited higher SUVBW than males. The techniques developed in this study may also be applied to further investigate the laterality and metabolism of other muscle groups.

• Wang, Yun; Nieuwenhuysen, Els Van; Rootwelt-Revheim, Mona-Elisabeth; Deroose, Christophe M.; Eriksson, Ane Gerda Zahl & Eyjólfsdóttir, Brynhildur [Show all 12 contributors for this article] (2025). First experience with intraperitoneal 224Ra-labeled microparticles after cytoreductive surgery in patients with peritoneal recurrence of platinum-sensitive epithelial ovarian cancer. Gynecologic Oncology. ISSN 0090-8258. 204, p. 158–164. doi: 10.1016/j.ygyno.2025.11.018. Full text in Research Archive Show summary

  Objective The aim of this Phase 1 study was to evaluate safety and tolerability of the alpha emitting therapy 224Ra-labeled microparticles (Radspherin®) and to establish the recommended dose for further development. Methods The study was conducted in patients who had undergone complete resection of platinum-sensitive recurrent ovarian cancer. A single dose of Radspherin was administered intraperitoneally one to three days after surgery. Dose escalation (3 + 3 design) was performed at 1, 2, 4 and 7 MBq. Safety and tolerability of Radspherin after 12 months are presented. Results Fourteen patients were enrolled across the 4 dose levels. Median age was 66 (56–77) years. Median peritoneal cancer index at the start of the surgery was 7 (3–16). No dose limiting toxicity (DLT) was observed. A total of 98 treatment emergent adverse events were reported (95 grade 1 or 2, and 3 grade 3). The three grade 3 events were cases of ileus (2) and anaemia (1) and were reported as unrelated to Radspherin by the investigators. One grade 2 serious adverse event of procedural complication (disconnect syringe-catheter) was reported as related to Radspherin. At 12-months, none of the patients had experienced peritoneal disease progression. Conclusions All dose levels were well tolerated, with no DLT observed. The highest activity dose of 7 MBq was selected as recommended dose for an expansion cohort. No grade ≥ 3 adverse events related to Radspherin were reported. Clinical trial information NCT03732768

• Tornes, Anna Julie Kjøl; Stenberg, Vilde Yuli; Liukaityte, Rugile; Llamazares, Ada Repetto; Qian, Peng & Wangen-Riise, Rina [Show all 10 contributors for this article] (2025). Optimizing [212Pb]Pb-AB001 Radiopharmaceutical Therapy Schedules in PSMA-Positive Subcutaneous Prostate Cancer Xenografts. Journal of Nuclear Medicine. ISSN 0161-5505. 66(12), p. 1956–1963. doi: 10.2967/jnumed.125.270444. Full text in Research Archive
• Tran-Gia, Johannes; Cicone, Francesco; Koole, Michel; Giammarile, Francesco; Gear, Jonathan & Deshayes, Emmanuel [Show all 20 contributors for this article] (2025). Rethinking Dosimetry: A European Perspective. Journal of Nuclear Medicine. ISSN 0161-5505. 66(9), p. 1323–1330. doi: 10.2967/jnumed.124.269378. Full text in Research Archive
• Tornes, Anna Julie Kjøl; Kvassheim, Monika; Ma, Li-Wei; Wiig, Elisabeth; Hillestad, Tiril & Rootwelt-Revheim, Mona-Elisabeth [Show all 9 contributors for this article] (2025). Therapeutic evaluation of [212Pb]Pb-AB001 and [177Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. 52, p. 4847–4859. doi: 10.1007/s00259-025-07330-y. Full text in Research Archive Show summary

  Background Metastatic castration-resistant prostate cancer (mCRPC) frequently leads to bone and soft tissue metastases, leading to poor prognosis. The beta-emitting radioligand [177Lu]Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA) and may be less efficient against micrometastatic disease. The alpha-emitting radioligand [212Pb]Pb-AB001 could offer enhanced treatment by delivering high energy over a short range. This study compared the efficacy of [212Pb]Pb-AB001 and [177Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. Methods Binding and internalisation of radioligands were evaluated in PC-3 PIP-luc cells. A mouse model was established by intracardiac injection of these cells. Treatments with 0.24‒1.0 MBq [212Pb]Pb-AB001 or 22‒66 MBq [177Lu]Lu-PSMA-617 were initiated 7 d post-cell inoculation. Metastatic burden was measured using bioluminescence imaging, and PSMA-targeted uptake was determined with [18F]F-PSMA-1007 µPET/µCT. Gamma-autoradiography evaluated [212Pb]Pb-AB001 distribution, and bone metastases were identified by radiography. Results Both radioligands displayed comparable in vitro binding. In vivo studies revealed metastatic formation in clinically relevant organs. µPET/µCT demonstrated increased [18F]F-PSMA-1007 uptake in metastases, matching the bioluminescence imaging results. Focal [212Pb]Pb-AB001 distribution in the metastatic xenograft indicated heterogeneously distributed micrometastases in the organs. A median survival up to 47 d was achieved with [212Pb]Pb-AB001, compared to 25 d for controls and 27 d for [177Lu]Lu-PSMA-617. An activity-dependent reduction in bone metastases was observed for [177Lu]Lu-PSMA-617, while no bone lesions were detected in [212Pb]Pb-AB001-treated mice. Conclusion [212Pb]Pb-AB001 showed significant efficacy against micrometastases and advantages over [177Lu]Lu-PSMA-617 in preventing or treating early bone metastases for the investigated injected activities. This implies clinical potential for treating mCRPC, including patients at risk of early metastatic disease, but further studies including dosimetry and toxicity analyses are required with regards to activity levels.

• Khatami, Seyed Sepehr; Shirkouhi, Samaneh Ghorbani; Høilund-Carlsen, Poul Flemming; Rootwelt-Revheim, Mona-Elisabeth; Alavi, Abass & Blaabjerg, Morten [Show all 7 contributors for this article] (2025). Peripheral Nervous System Complications after COVID-19 Vaccination. Journal of Integrative Neuroscience (JIN). ISSN 0219-6352. 24(3). doi: 10.31083/JIN26632. Full text in Research Archive
• Fagerland, Steffen Knut Maude; Løve, Andreas; Helliesen, Tord K.; Martinsen, Ørjan Grøttem; Rootwelt-Revheim, Mona-Elisabeth & Endestad, Tor (2025). Method for Using Functional Near-Infrared Spectroscopy (fNIRS) to Explore Music-Induced Brain Activation in Orchestral Musicians in Concert. Sensors. 25(6). doi: 10.3390/s25061807. Full text in Research Archive
• Ghonim, Mohamed; Redden, Hyae Won Kim; Gharavi, Daniel; Mamidi, Ramya S.; Patel, Dev A. & Mirbod, Melika [Show all 11 contributors for this article] (2025). Structural and Molecular Imaging of Aging Brain: A Focus on MR Imaging and PET Modalities. PET Clinics. ISSN 1556-8598. 20(1), p. 67–88. doi: 10.1016/j.cpet.2024.09.007. Full text in Research Archive
• Kepp, Kasper P.; Høilund-Carlsen, Poul F.; Cristea, Ioana A.; Cumming, Robert G.; Daly, Timothy & Emilsson, Louise [Show all 16 contributors for this article] (2025). Communicating scientific evidence: drugs for Alzheimer’s disease as a case study. Current Medical Research and Opinion. ISSN 0300-7995. 41(2), p. 347–354. doi: 10.1080/03007995.2025.2458530. Full text in Research Archive
• Singh, Shashi B.; Bhandari, Sambhawana; Bhandari, Sadikshya; Bhandari, Samikshya; Singh, Rajshree & Raynor, William Y. [Show all 10 contributors for this article] (2024). Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review. Annals of Nuclear Medicine. ISSN 0914-7187. doi: 10.1007/s12149-023-01896-z. Full text in Research Archive Show summary

  Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

• Gujral, Jaskeerat; Gandhi, Om H; Singh, Shashi B.; Ahmed, Malia; Ayubcha, Cyrus & Werner, Thomas J. [Show all 8 contributors for this article] (2024). PET, SPECT, and MRI imaging for evaluation of Parkinson’s disease. The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI). doi: 10.62347/AICM8774. Full text in Research Archive
• Teichner, Eric M.; Subtirelu, Robert C.; Patil, Shiv; Parikh, Chitra; Ashok, Arjun B. & Talasila, Sahithi [Show all 12 contributors for this article] (2024). Positron Emission Tomography (PET) in presurgical planning of anterior temporal lobectomy: A systematic review of efficacy and limitations. Clinical neurology and neurosurgery (Dutch-Flemish ed. Print). ISSN 0303-8467. 246. doi: 10.1016/j.clineuro.2024.108562. Full text in Research Archive Show summary

  Introduction Temporal lobe epilepsy (TLE), a debilitating neurological disorder, necessitates refined diagnostic and treatment strategies. This comprehensive review appraises the potential of positron emission tomography (PET) in enhancing the presurgical planning of Anterior Temporal Lobectomy (ATL) for patients afflicted with TLE. Methods A comprehensive literature search was conducted using the PubMed, SCOPUS, and ScienceDirect databases from 1985 to 2022, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies investigating PET and ATL. This review studied a range of radiotracers, including FDG, H2O, FMZ, MPPF, and FCWAY, analyzing their efficacy in detecting epileptogenic foci, establishing resection boundaries, and predicting postoperative outcomes. The study paid special attention to cases where MRI findings were inconclusive. Results A total of 52 studies were included in the final analysis. Our analysis revealed that FDG-PET imaging was instrumental in identifying seizure foci and predicting postoperative results. It exhibited significant value in situations where structural abnormalities were absent on MRI scans. Furthermore, newer radiotracers such as 5-HT1A antagonists, FCWAY and MPPF, presented promising potential for localizing seizure foci, particularly in MRI-negative TLE, despite their comparatively limited current usage. Conclusion PET imaging, although challenged by issues such as radiation exposure, limited accessibility, and high costs, offers considerable promise. Integration with other imaging modalities, such as EEG and MRI, has contributed to improved localization of epileptogenic foci and subsequently, enhanced surgical outcomes. Further research must focus on establishing the relative efficacy and optimal combinations of these radiotracers in the orchestration of ATL surgical planning and prognostication of postoperative outcomes for TLE patients. Encouragingly, these advancements hold the potential to revolutionize the management of TLE, delivering a better quality of life for patients.

• Khatami, Seyed Sepehr; Rootwelt-Revheim, Mona-Elisabeth; Høilund-Carlsen, Poul Flemming; Alavi, Abass; Shirkouhi, Samaneh Ghorbani & Andalib, Sasan (2024). Central nervous system manifestations following vaccination against COVID-19. Brain, Behavior, and Immunity - Health (BBI - Health). 38. doi: 10.1016/j.bbih.2024.100788. Full text in Research Archive Show summary

  Coronavirus disease 2019 (COVID-19) vaccination has become the most effective countermeasure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, vaccination is associated with side effects. This narrative review focuses on central nervous system (CNS) manifestations following COVID-19 vaccination and provides a summary of the potential underlying mechanisms and methods of diagnosis and management of the vaccination-related CNS manifestations. Headache, myalgia, optic neuritis, seizure, multiple sclerosis, acute disseminated encephalomyelitis and encephalitis, delirium, acute transverse myelitis, and stroke have been reported after COVID-19 vaccination. Constant headache and myalgia are common manifestations that may necessitate further clinical investigation for stroke. To limit consequences, it is imperative to follow standard treatment protocols for each neurological disorder following COVID-19 vaccination. Immunosuppressive medication can be helpful in the treatment of seizures following vaccination since the immune response is involved in their etiology. Clinicians should be aware of the manifestations after COVID-19 vaccination to respond promptly and effectively. Clinical guidelines for the management of CNS manifestations following COVID-19 vaccination are in high demand and would be useful in each new SARS-CoV-2 variant pandemic.

• Andel, Peter Michael; Aamodt, Anne Hege; Gleditsch, Jostein; Melin, Erik; Rootwelt-Revheim, Mona-Elisabeth & Steine, Kjetil [Show all 7 contributors for this article] (2024). Elective Direct Current Cardioversion of Atrial Fibrillation: Silent Brain Infarction and Health-Related Quality of Life. Cardiology. ISSN 0008-6312. 149(6), p. 571–579. doi: 10.1159/000540007. Full text in Research Archive Show summary

  Introduction: Atrial fibrillation (AF) increases the risk for stroke, dementia, and impaired health-related quality of life (HRQL). Elective direct current cardioversion (ECV) is often used to restore sinus rhythm but is associated with thromboembolism. While larger strokes usually produce symptoms, subclinical ones may go unrecognized and may cause cognitive and functional decline over time. In the current study, we sought to evaluate the effects of ECV on silent brain infarctions and HRQL in patients with AF. Methods: Patients with AF (n = 46) underwent brain magnetic resonance imaging (MRI) and HRQL assessment using the EuroQL-5D5L questionnaire before and after ECV. Implantable loop recorders (ILRs) were used to observe the rate of early AF recurrences within the first 30 days. All patients were treated with anticoagulants according to guidelines. The primary endpoint was silent brain infarction assessed by brain MRI within the first 2 weeks after ECV. Secondary endpoints were the change in HRQL and its association with AF recurrence at follow-up and by ILR recordings. Results: New silent brain infarction after ECV was detected in 1 patient. At follow-up visit after 19.1 days AF recurrence was detected by 12-lead ECG in 13 patients (28.3%), whereas 27 patients (58.7%) had AF recurrence recorded by ILR within the first 30 days after ECV. European Heart Rhythm Association (EHRA) symptom score and the EuroQL-5d5L score were improved after ECV. Conclusion: Silent brain infarctions may occur after ECV despite anticoagulation treatment. Early AF recurrence is frequent. ECV positively affects HRQL mainly in those patients with sustained sinus rhythm at follow-up.

• Mirbod, Melika; Ayubcha, Cyrus; Redden, Hyae Won Kim; Teichner, Eric; Subtirelu, Robert C. & Patel, Raj [Show all 10 contributors for this article] (2024). FDG-PET in the diagnosis of primary progressive aphasia: a systematic review. Annals of Nuclear Medicine. ISSN 0914-7187. doi: 10.1007/s12149-024-01958-w. Full text in Research Archive Show summary

  Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer’s disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions.

• Singh, Shashi B.; Tiwari, Atit; Katta, Maanya R.; Kafle, Riju; Ayubcha, Cyrus & Patel, Krishna H. [Show all 10 contributors for this article] (2024). The utility of PET imaging in depression. Frontiers in Psychiatry. 15. doi: 10.3389/fpsyt.2024.1322118. Full text in Research Archive Show summary

  This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

• Singh, Shashi B; Shrestha, Niki; Bhandari, Sadikshya; Shrestha, Suprita; Shrestha, Bijay & Shrestha, Neharika [Show all 12 contributors for this article] (2024). [ 18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO). The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI). doi: 10.62347/OQQC6007. Full text in Research Archive Show summary

  Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

• Høilund-Carlsen, Poul F.; Alavi, Abass; Barrio, Jorge R.; Castellani, Rudolph J.; Costa, Tommaso & Herrup, Karl [Show all 13 contributors for this article] (2024). Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit. Ageing Research Reviews. ISSN 1568-1637. 99. doi: 10.1016/j.arr.2024.102348. Full text in Research Archive
• Singh, Shashi B.; Bhattarai, Yash; Kafle, Riju; Panta, Marvi; Tiwari, Atit & Ayubcha, Cyrus [Show all 9 contributors for this article] (2024). A Brief History and the Use of PET in the Diagnosis and Management of Schizophrenia: An Educational Review. PET Clinics. ISSN 1556-8598. 20(1), p. 11–24. doi: 10.1016/j.cpet.2024.09.005. Full text in Research Archive
• Talasila, Sahithi; Teichner, Eric M.; Subtirelu, Robert C.; Talasila, Naga Chaitanya P.; Mannam, Sricharvi & Werner, Thomas [Show all 8 contributors for this article] (2024). Comprehensive considerations for dermatologists: the application of FDG-PET in evaluating cutaneous lesions in pediatric Langerhans cell histiocytosis. Frontiers of Medicine. ISSN 2095-0217. doi: 10.3389/fmed.2024.1378638. Full text in Research Archive Show summary

  Langerhans cell histiocytosis (LCH) is a complex disorder characterized by the clonal proliferation of Langerhans cells, primarily affecting children and adolescents. This condition exhibits a wide spectrum of clinical presentations, necessitating a multidisciplinary approach for diagnosis, treatment, and follow-up. Cutaneous manifestations of LCH are significant, mimicking common dermatoses and posing diagnostic challenges. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) has emerged as an important tool in the evaluation of pediatric LCH, offering insights into disease activity, extent, and therapeutic response. Moreover, FDG-PET provides a non-invasive means to distinguish between active LCH skin lesions and other dermatological conditions with similar clinical appearances, enhancing diagnostic accuracy and aiding in disease monitoring. This educational review summarizes the utility of nuclear imaging techniques, with a focus on PET scans, in the diagnosis and management of cutaneous pediatric LCH. A comprehensive literature search identified seven relevant articles, including retrospective studies and case reports. These studies highlight the efficacy of FDG-PET in localizing active LCH skin lesions, monitoring disease activity, and guiding treatment decisions. FDG-PET represents a valuable imaging modality for dermatologists, oncologists, and pediatricians managing pediatric LCH patients with cutaneous involvement. This non-invasive technique contributes to improved diagnostic accuracy and facilitates early intervention, ultimately enhancing patient care and outcomes.

• Müller, Ebba Gløersen; Dahlberg, Daniel; Hassel, Bjørnar; Rootwelt-Revheim, Mona-Elisabeth & Connelly, James Pattrick (2024). Brain Abscess Causes Brain Damage With Long-Lasting Focal Cerebral Hypoactivity that Correlates With Abscess Size: A Cross-Sectional 18F-Fluoro-Deoxyglucose Positron Emission Tomography Study. Neurosurgery. ISSN 0148-396X. doi: 10.1227/neu.0000000000003268. Full text in Research Archive Show summary

  BACKGROUND AND OBJECTIVES: Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess. METHODS: 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess. RESULTS: FDG-PET/CT revealed hypometabolism in the neocortex or cerebellum overlying the previous bacterial abscess in 38 of 40 patients. The larger the abscess, the greater was the extent of the subsequent hypometabolism (r = 0.63; p = 3 × 10 5). In 9 patients, the extent of subsequent hypometabolism seemed to coincide with the extent of peri-abscess edema in the acute phase. Follow-up MRI after ≥1 year in 9 patients showed focal tissue loss and gliosis. In 13 patients with abnormal electroencephalography recordings, abnormalities extended beyond the cerebral lobe affected by the abscess, indicating damage to wider brain networks. The abscess capsule had an FDG signal indicating inflammation only during the first week after neurosurgical pus drainage. CONCLUSION: The bigger a brain abscess is allowed to grow, the more extensive is the long-term focal reduction in brain activity. This finding emphasizes the need for rapid neurosurgical intervention. The abscess capsule does not display long-lasting inflammation and probably does not explain long-term symptoms after brain abscess.

• Glennan, Patrick; Shehu, Vanessa; Singh, Shashi B.; Werner, Thomas J.; Alavi, Abass & Rootwelt-Revheim, Mona-Elisabeth (2024). PET Imaging in Chimeric Antigen Receptor T-Cell Trafficking. PET Clinics. ISSN 1556-8598. 19(4), p. 569–576. doi: 10.1016/j.cpet.2024.06.002. Full text in Research Archive
• Fagerland, Steffen Knut Maude; Berntsen, Henrik Røsholm; Fredriksen, Mats; Endestad, Tor; Skouras, Stavros & Rootwelt-Revheim, Mona-Elisabeth [Show all 7 contributors for this article] (2024). Exploring protocol development: Implementing systematic contextual memory to enhance real-time fMRI neurofeedback. Journal of Electrical Bioimpedance. 15(1), p. 41–62. doi: 10.2478/joeb-2024-0006. Full text in Research Archive Show summary

  Objective: The goal of this study was to explore the development and implementation of a protocol for real-time fMRI neurofeedback (rtfMRI-nf) and to assess the potential for enhancing the selective brain activation using stimuli from Virtual Reality (VR). In this study we focused on two specific brain regions, supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). Publications by other study groups have suggested impaired function in these specific brain regions in patients with the diagnoses Attention Deficit Hyperactivity Disorder (ADHD) and Tourette’s Syndrome (TS). This study explored the development of a protocol to investigate if attention and contextual memory may be used to systematically strengthen the procedure of rtfMRI-nf. Methods: We used open-science software and platforms for rtfMRI-nf and for developing a simulated repetition of the rtfMRI-nf brain training in VR. We conducted seven exploratory tests in which we updated the protocol at each step. During rtfMRI-nf, MRI images are analyzed live while a person is undergoing an MRI scan, and the results are simultaneously shown to the person in the MRI-scanner. By focusing the analysis on specific regions of the brain, this procedure can be used to help the person strengthen conscious control of these regions. The VR simulation of the same experience involved a walk through the hospital toward the MRI scanner where the training sessions were conducted, as well as a subsequent simulated repetition of the MRI training. The VR simulation was a 2D projection of the experience. The seven exploratory tests involved 19 volunteers. Through this exploration, methods for aiming within the brain (e.g. masks/algorithms for coordinate-system control) and calculations for the analyses (e.g. calculations based on connectivity versus activity) were updated by the project team throughout the project. The final procedure involved three initial rounds of rtfMRI-nf for learning brain strategies. Then, the volunteers were provided with VR headsets and given instructions for one week of use. Afterward, a new session with three rounds of rtfMRI-nf was conducted. Results: Through our exploration of the indirect effect parameters – brain region activity (directed oxygenated blood flow), connectivity (degree of correlated activity in different regions), and neurofeedback score – the volunteers tended to increase activity in the reinforced brain regions through our seven tests. Updates of procedures and analyses were always conducted between pilots, and never within. The VR simulated repetition was tested in pilot 7, but the role of the VR contribution in this setting is unclear due to underpowered testing. Conclusion: This proof-of-concept protocol implies how rtfMRI-nf may be used to selectively train two brain regions (SMA and rIFG). The method may likely be adapted to train any given region in the brain, but readers are advised to update and adapt the procedure to experimental needs.

• Høilund-Carlsen, Poul F.; Alavi, Abass; Castellani, Rudolph J.; Neve, Rachael L.; Perry, George & Rootwelt-Revheim, Mona-Elisabeth [Show all 7 contributors for this article] (2024). Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? International Journal of Molecular Sciences. ISSN 1661-6596. 25(7). doi: 10.3390/ijms25073892. Full text in Research Archive Show summary

  The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

• Larsen, Stein Gunnar; Graf, W.; Larsen, R.H.; Rootwelt-Revheim, Mona-Elisabeth; Mariathasan, Anthony Burton & Sørensen, Olaf [Show all 12 contributors for this article] (2024). Eighteen-Months Safety and Efficacy Following Intraperitoneal Treatment With 224Radium-Labeled Microparticles After CRS-HIPEC in Patients With Peritoneal Metastasis From Colorectal Cancer. Journal of Surgical Oncology. ISSN 0022-4790. 130(6), p. 1395–1402. doi: 10.1002/jso.27897. Full text in Research Archive Show summary

  Background and Objectives Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. Methods A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. Results Eleven patients received 1−4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. Conclusions Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.

• Høilund-Carlsen, Poul F.; Rootwelt-Revheim, Mona Elisabeth; Costa, Tommaso; Alavi, Abass; Kepp, Kasper P. & Sensi, Stefano L. [Show all 10 contributors for this article] (2023). Passive Alzheimer's immunotherapy: A promising or uncertain option? Ageing Research Reviews. ISSN 1568-1637. 90. doi: 10.1016/j.arr.2023.101996. Full text in Research Archive
• Larsen, Stein Gunnar; Graf, Wilhelm; Mariathasan, Anthony Burton; Sørensen, Olaf; Spasojevic, Milan & Goscinski, Mariusz Adam [Show all 11 contributors for this article] (2023). First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study). Frontiers in Medicine. 10. doi: 10.3389/fmed.2023.1070362. Full text in Research Archive Show summary

  Background: Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11–12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC. Methods: A first-in-human phase 1 study (EudraCT 2018–002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented. Results: Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28–78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3–30). The peritoneal cancer index was median 7 (3–19), operation time was 395 min (194–515), and hospital stay was 12 days (7–37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution. Conclusion: All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.

• Subtirelu, Robert C.; Teichner, Eric M.; Ashok, Arjun; Parikh, Chitra; Talasila, Sahithi & Matache, Irina-Mihaela [Show all 14 contributors for this article] (2023). Advancements in dendritic cell vaccination: enhancing efficacy and optimizing combinatorial strategies for the treatment of glioblastoma. Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1271822. Full text in Research Archive Show summary

  Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18 F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

• Nørgaard, Jakob Nordberg; Abildgaard, Niels; Lysén, Anna Karin Christina; Tsykunova, Galina; Vangsted, Annette Juul & João, Cristina [Show all 13 contributors for this article] (2023). Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation. Leukemia. ISSN 0887-6924. 37, p. 2107–2114. doi: 10.1038/s41375-023-01998-7. Full text in Research Archive
• Evanson, D.; Griffin, M.; O’Reilly, S.E.; Johnson, T.; Werner, T. & Kothekar, E. [Show all 13 contributors for this article] (2023). Comparative assessment of radiation therapy–induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. doi: 10.1007/s00259-023-06535-3. Full text in Research Archive Show summary

  Abstract Purpose To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18 F-fluoro-D-deoxyglucose ([ 18 F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. Method Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton ( n  = 27) or photon ( n  = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [ 18 F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t -tests. Results RT treatments were associated with increased SUVmeans in the AA, DA, and AoA—1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean − pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA ( p  = 0.043) and AoA ( p  = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. Conclusion Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. Trial registration NCT02135679.

• Singh, Shashi B.; Bhandari, Sadikshya; Siwakoti, Shisir; Bhatta, Rabi; Raynor, William Y. & Werner, Thomas J. [Show all 9 contributors for this article] (2023). Is Imaging Bacteria with PET a Realistic Option or an Illusion? Diagnostics (Basel). 13(7). doi: 10.3390/diagnostics13071231. Full text in Research Archive Show summary

  The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

• Høilund-Carlsen, Poul F.; Piri, Reza; Gerke, Oke; Sturek, Michael; Werner, Thomas J. & Rootwelt-Revheim, Mona Elisabeth [Show all 7 contributors for this article] (2023). NaF-PET Imaging of Atherosclerosis Burden. Journal of Imaging. 9(2), p. 1–18. doi: 10.3390/jimaging9020031. Full text in Research Archive Show summary

  The method of 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) of atherosclerosis was introduced 12 years ago. This approach is particularly interesting because it demonstrates microcalcification as an incipient sign of atherosclerosis before the development of arterial wall macrocalcification detectable by CT. However, this method has not yet found its place in the clinical routine. The more exact association between NaF uptake and future arterial calcification is not fully understood, and it remains unclear to what extent NaF-PET may replace or significantly improve clinical cardiovascular risk scoring. The first 10 years of publications in the field were characterized by heterogeneity at multiple levels, and it is not clear how the method may contribute to triage and management of patients with atherosclerosis, including monitoring effects of anti-atherosclerosis intervention. The present review summarizes findings from the recent 2¾ years including the ability of NaF-PET imaging to assess disease progress and evaluate response to treatment. Despite valuable new information, pertinent questions remain unanswered, not least due to a pronounced lack of standardization within the field and of well-designed long-term studies illuminating the natural history of atherosclerosis and effects of intervention.

• Delman, Allegra; Griffin, Matthew T.; Werner, Thomas J.; Alavi, Abass; Raynor, William Y. & Rootwelt-Revheim, Mona Elisabeth (2023). The emerging role of positron emission tomography (PET) in the management of photon radiotherapy-induced vasculitis in head and neck cancer patients. Clinical and translational imaging. ISSN 2281-5872. 11(2), p. 157–164. doi: 10.1007/s40336-023-00541-z. Full text in Research Archive Show summary

  Abstract Purpose While radiotherapy (RT) for head and neck cancer (HNC) has made recent strides, RT-induced vasculitis continues to adversely affect long-term patient outcomes. Guidelines for managing this complication remain scarce, supporting the need for a sensitive imaging modality in post-treatment evaluations. In this review, we discuss the current literature regarding 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 18 F-sodium fluoride (NaF-PET) in evaluating RT-induced vasculitis in HNC patients, highlighting several arenas of evolving clinical significance: (1) early recognition and standardized evaluation of RT-induced vasculitis, and (2) potential for a multifaceted diagnostic tool to stratify cardiovascular risk in HNC patients. Methods Numerous databases, including, but not limited to, Google Scholar and PubMed, were utilized to compile a body of literature regarding PET imaging of RT-induced vasculitis in HNC and related malignancies. Results Multiple studies have established the clinical capabilities of FDG-PET/computed tomography (FDG-PET/CT) for detection and management of RT-induced vasculitis in HNC patients, while NaF-PET/CT remains under investigation. Inflammatory vascular stages may be best analyzed by FDG-PET/CT, while vascular microcalcification and atherosclerotic disease may be supplementally assessed by the unique properties of NaF-PET/CT. With these modalities detecting primary stages of more detrimental vascular complications, PET imaging may carry several advantages over conventional, structural techniques. Conclusion FDG-PET/CT and NaF-PET/CT hold significant potential as preliminary diagnostic tools in monitoring early inflammation and atherosclerotic plaque development, warranting further research and attention. Applying these techniques in this context may foster proactive and consistent assessments of RT-induced vasculitis in HNC patients, mitigating potential cardiovascular risks through better-informed treatment decisions.

• Juzenienne, Asta; Stenberg, Vilde Yuli; Bruland, Øyvind; Rootwelt-Revheim, Mona Elisabeth & Larsen, Roy Hartvig (2023). Dual targeting with 224Ra/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach. Frontiers in Medicine. 9:1051825, p. 1–12. doi: 10.3389/fmed.2022.1051825. Full text in Research Archive Show summary

  Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking 224 Ra and cell-directed complexes of progeny 212 Pb is a promising approach to treat metastatic cancers with bone and soft tissue lesions as well as skeletal metastases of mixed lytic/osteoblastic nature. A novel liquid 224 Ra/ 212 Pb-generator for rapid preparation of a dual targeting solution is described. Cancer cell targeting monoclonal antibodies, their fragments, synthetic proteins or peptides can all be radiolabeled with 212 Pb in the 224 Ra-solution in transient equilibrium with daughter nuclides. Thus, 224 Ra targets stromal elements in sclerotic bone metastases and 212 Pb-chelated-conjugate targets tumor cells of metastatic prostate cancer or osteosarcoma. The dual targeting solution may also be explored to treat metastatic breast cancer or multiple myeloma after manipulation of bone metastases to a more osteoblastic phenotype by the use of bisphosphonates, denosumab, bortezomib or hormone therapy prior to treatment. This may improve targeting of bone-seeking 224 Ra and render an augmented radiation dose deposited within metastases. Our preliminary preclinical studies provide conceptual evidence that the dual 224 Ra-solution with bone or tumor-targeted delivery of 212 Pb has potential to inhibit cancer metastases without significant toxicity. In some settings, the use of a booster dose of purified 212 Pb-conjugate alone could be required to elevate the effect of this tumor cell directed component, if needed, e.g., in a fractionated treatment regimen, where the dual targeting solution will act as maintenance treatment.

• Talasila, Sahithi; Teichner, Eric M.; Subtirelu, Robert C.; Xiang, David H.; Ayubcha, Cyrus & Werner, Thomas [Show all 8 contributors for this article] (2023). The Role of FDG-PET in the Evaluation of Hidradenitis Suppurativa: A Systematic Review. Journal of Clinical Medicine. 12(17). doi: 10.3390/jcm12175491. Full text in Research Archive Show summary

  Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by nodules, comedones, and sinus tracts that often leave prominent scarring. In recent years, non-invasive imaging techniques have been used to assess the inflammatory activity, vascularization, and treatment response of lesions. Specifically, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans may aid in identifying systemic inflammation in patients with HS, improving diagnosis. Inflamed hypermetabolic tissues exhibit a greater uptake of FDG due to increased glucose uptake and vascularity. A systematic review was conducted to summarize the utility of nuclear imaging techniques in the diagnosis and treatment follow-up of HS. PubMed, Scopus, and ScienceDirect databases were utilized for relevant articles discussing the utility of PET scans in managing HS. A total of 51 citations were identified in the initial search. Following the review of titles, abstracts, and duplicates, 43 articles were excluded, leaving a total of eight articles for analysis. Data were extracted from each article, encompassing the number of patients, imaging techniques employed, and final results. An analysis of the data demonstrated that FDG-PET showed evidence of identifying subclinical lesions of the disease, improving the visualization of HS, and providing an objective method of assessing severity.

• Mamidi, Ramya S.; Ayubcha, Cyrus; Rigney, Grant; Kirschner, Jason; Gerke, Oke & Werner, Thomas J. [Show all 9 contributors for this article] (2023). A prospective 18 F-fluorodeoxyglucose positron emission tomography/computed tomography study of the neurometabolic effects in cocaine use and HIV infection. AIDS (London). ISSN 0269-9370. 37(6), p. 905–912. doi: 10.1097/QAD.0000000000003485. Full text in Research Archive Show summary

  Objectives: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in cocaine users with HIV infection. Design: Sixty-three participants were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV−) individuals. Each group was further split into cocaine users (CO+) and non-cocaine users (CO−). Of the HIV+, half were cocaine users and half were not. Of the HIV−, 14 were cocaine users and 13 were not. 18F-FDG-PET and low dose CT scans were performed on all participants. Methods: Brain glucose metabolism was evaluated by 18F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 min after injection. ROVER software was used for image analysis and regions of interest masks were applied via an adaptive threshold system. ANOVA tests and t-tests were performed to assess the respective differences between the four groups. Results: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV−/CO− group (group D) showed the highest; the HIV+/CO− and HIV−/CO+ groups (groups B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum. Conclusion: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18F-FDG uptake.

• Hameed, Rizwanullah; Bahadur, Anuradha Rosario; Singh, Shashi Bhushan; Sher, Juwairah; Todua, Maia & Moradi, Leah [Show all 14 contributors for this article] (2023). Neurological and Psychiatric Manifestations of Long COVID-19 and Their (18F)FDG PET Findings: A Review. Diagnostics (Basel). 13(14). doi: 10.3390/diagnostics13142353. Full text in Research Archive Show summary

  For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed “long COVID-19”. The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

• Jenul, Anna; Stokmo, Henning Langen; Schrunner, Stefan; Hjortland, Geir Olav; Rootwelt-Revheim, Mona-Elisabeth & Tomic, Oliver (2023). Novel ensemble feature selection techniques applied to high-grade gastroenteropancreatic neuroendocrine neoplasms for the prediction of survival. Computer Methods and Programs in Biomedicine. ISSN 0169-2607. 244. doi: 10.1016/j.cmpb.2023.107934. Full text in Research Archive Show summary

  • We model and predict the overall survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms. • Novel ensemble feature selectors RENT and UBayFS are assessed for predictive performance, stability, and interpretability. • Data- as well as expert-driven feature selection (with and without prior knowledge) are evaluated. • Our results show that both methods allow accurate predictions and have a stabilizing effect on the model parameters. • RENT and UBayFS identify influencing factors for overall survival and support clinical experts in decision-making.

• Lysvik, Elisabeth Kirkeby; Mikalsen, Lars Tore Gyland; Rootwelt-Revheim, Mona Elisabeth; Emblem, Kyrre Eeg & Hjørnevik, Trine (2023). Optimization of Q.Clear reconstruction for dynamic 18F PET imaging. EJNMMI Physics. ISSN 2197-7364. 10(1), p. 1–13. doi: 10.1186/s40658-023-00584-1. Full text in Research Archive Show summary

  Background: Q.Clear, a Bayesian penalized likelihood reconstruction algorithm, has shown high potential in improving quantitation accuracy in PET systems. The Q.Clear algorithm controls noise during the iterative reconstruction through a β penalization factor. This study aimed to determine the optimal β-factor for accurate quantitation of dynamic PET scans. Methods: A Flangeless Esser PET Phantom with eight hollow spheres (4-25 mm) was scanned on a GE Discovery MI PET/CT system. Data were reconstructed into five sets of variable acquisition times using Q.Clear with 18 different β-factors ranging from 100 to 3500. The recovery coefficient (RC), coefficient of variation (CVRC) and root-mean-square error (RMSERC) were evaluated for the phantom data. Two male patients with recurrent glioblastoma were scanned on the same scanner using 18F-PSMA-1007. Using an irreversible two-tissue compartment model, the area under curve (AUC) and the net influx rate Ki were calculated to assess the impact of different β-factors on the pharmacokinetic analysis of clinical PET brain data. Results: In general, RC and CVRC decreased with increasing β-factor in the phantom data. For small spheres (

• McDonald, Elysia O.; Amanullah, Amir A.; Park, Peter Sang Uk; Song, William; Werner, Thomas J. & Alavi, Abass [Show all 7 contributors for this article] (2023). The role of 18F-FDG PET/CT in primary cutaneous lymphoma: an educational review. Annals of Nuclear Medicine. ISSN 0914-7187. 37(6), p. 328–348. doi: 10.1007/s12149-023-01830-3. Full text in Research Archive Show summary

  Abstract Introduction Primary cutaneous lymphoma (PCL) is a cutaneous non-Hodgkin’s lymphoma that originates in the skin and lacks extracutaneous spread upon initial diagnosis. The clinical management of secondary cutaneous lymphomas is different from that of PCLs, and earlier detection is associated with better prognosis. Accurate staging is necessary to determine the extent of disease and to choose the appropriate treatment. The aim of this review is to investigate the current and potential roles of 18 F- fluorodeoxyglucose positron emission tomography–computed tomography ( 18 F-FDG PET/CT) in the diagnosis, staging, and monitoring of PCLs. Methods A focused review of the scientific literature was performed using inclusion criteria to filter results pertaining to human clinical studies performed between 2015 and 2021 that analyzed cutaneous PCL lesions on 18 F PET/CT imaging. Results &amp; Conclusion A review of 9 clinical studies published after 2015 concluded that 18 F-FDG PET/CT is highly sensitive and specific for aggressive PCLs and proved valuable for identifying extracutaneous disease. These studies found 18 F-FDG PET/CT highly useful for guiding lymph node biopsy and that imaging results influenced therapeutic decision in many cases. These studies also predominantly concluded that 18 F-FDG PET/CT is more sensitive than computed tomography (CT) alone for detection of subcutaneous PCL lesions. Routine revision of nonattenuation-corrected (NAC) PET images may improve the sensitivity of 18 F-FDG PET/CT for detection of indolent cutaneous lesions and may expand the potential uses of 18 F-FDG PET/CT in the clinic . Furthermore, calculating a global disease score from 18 F-FDG PET/CT at every follow-up visit may simplify assessment of disease progression in the early clinical stages, as well as predict the prognosis of disease in patients with PCL.

• Griffin, Matthew T.; Werner, Thomas J.; Alavi, Abass & Rootwelt-Revheim, Mona Elisabeth (2023). The value of FDG-PET/CT imaging in the assessment, monitoring, and management of COVID-19. The European Physical Journal Plus. 138(283), p. 1–9. doi: 10.1140/epjp/s13360-023-03797-6. Full text in Research Archive Show summary

  Abstract The pathogenesis of Coronavirus Disease 2019 (COVID-19) involves cytokine-driven recruitment and accumulation of inflammatory cells at sites of infection. These activated neutrophils, monocytes, and effector T cells are highly glycolytic and thus appear as [18]F-labeled fluorodeoxyglucose (FDG) avid sites on positron emission tomography (PET) imaging. FDG-PET-computed tomography (FDG-PET/CT) is a highly sensitive modality for the detection, monitoring, and assessing response related to COVID-19 disease activity that holds significant clinical relevance. To date, concerns over cost, access, and undue radiation exposure have limited the use of FDG-PET/CT in COVID-19 to a small number of individuals where PET-based interventions were already indicated. In this review, we summarize the existing literature on the use of FDG-PET in the detection and monitoring of COVID-19 with particular focus on several areas of clinical relevance that warrant future research: (1) incidental early detection of subclinical COVID-19 in patients who have undergone FDG-PET for other underlying diseases, (2) standardized quantitative assessment of COVID-19 disease burden at specific points in time, and (3) analysis of FDG-PET/CT data leading to better characterization of COVID-19 pathogenesis. Employing FDG-PET/CT for these purposes may allow for the earliest detection of COVID-19-associated venous thromboembolism (VTE), standardized monitoring of disease progression and response to treatment, and better characterization of the acute and chronic complications of this disease.

• Høilund-Carlsen, Poul F.; Rootwelt-Revheim, Mona Elisabeth; Costa, Tommaso; Kepp, Kasper P.; Castellani, Rudolph J. & Perry, George [Show all 8 contributors for this article] (2023). FDG-PET versus Amyloid-PET Imaging for Diagnosis and Response Evaluation in Alzheimer’s Disease: Benefits and Pitfalls. Diagnostics (Basel). 13(13). doi: 10.3390/diagnostics13132254. Full text in Research Archive Show summary

  In June 2021, the US Federal Drug and Food Administration (FDA) granted accelerated approval for the antibody aducanumab and, in January 2023, also for the antibody lecanemab, based on a perceived drug-induced removal of cerebral amyloid-beta as assessed by amyloid-PET and, in the case of lecanemab, also a presumption of limited clinical efficacy. Approval of the antibody donanemab is awaiting further data. However, published trial data indicate few, small and uncertain clinical benefits, below what is considered “clinically meaningful” and similar to the effect of conventional medication. Furthermore, a therapy-related decrease in the amyloid-PET signal may also reflect increased cell damage rather than simply “amyloid removal”. This interpretation is more consistent with increased rates of amyloid-related imaging abnormalities and brain volume loss in treated patients, relative to placebo. We also challenge the current diagnostic criteria for AD based on amyloid-PET imaging biomarkers and recommend that future anti-AD therapy trials apply: (1) diagnosis of AD based on the co-occurrence of cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, (2) therapy efficacy determined by favorable effect on cognitive ability, cerebral metabolism by FDG-PET, and brain volumes by MRI, and (3) neuropathologic examination of all deaths occurring in these trials.

• Teichner, Eric M.; Subtirelu, Robert C.; Ashok, Arjun; Su, Yvonne; Anderson, Victoria & Writer, Milo [Show all 13 contributors for this article] (2023). The Emerging Role of NaF-PET/CT in Detecting Vascular Microcalcification in the Pathogenesis of Neurological Dysfunction. Journal of Vascular Diseases. 2(3), p. 310–316. doi: 10.3390/jvd2030023. Full text in Research Archive
• Reddy, Natasha; Raynor, William Y.; Werner, Thomas J.; Baker, Joshua F.; Alavi, Abass & Rootwelt-Revheim, Mona Elisabeth (2023). 18F-FDG and 18F-NaF PET/CT Global Assessment of Large Joint Inflammation and Bone Turnover in Rheumatoid Arthritis. Diagnostics (Basel). 13(13). doi: 10.3390/diagnostics13132149. Full text in Research Archive Show summary

  Rheumatoid arthritis (RA) involves chronic inflammation of synovial joints, causing pain, stiffness, and limited mobility. 18F-sodium fluoride (NaF) is a PET tracer whose uptake reflects bone turnover, while 18F-fludeoxyglucose (FDG) shows glucose metabolism and can serve as a marker for inflammation. The aim of this study is to determine the feasibility of calculating the FDG and NaF mean standardized uptake value (SUVmean) in the knee joint, hip joint, and sacroiliac (SI) joint of RA patients and to determine their association with patient characteristics. Prospective FDG-PET/CT as well as NaF-PET/CT imaging was performed on 18 RA patients. The global SUVmean was calculated on FDG-PET/CT and NaF-PET/CT images using a semiautomated CT-based method of segmentation. FDG and NaF uptake were found to be significantly correlated in the knee (r = 0.77, p &lt; 0.001), but not in the hip and SI joints. In the knee, both NaF SUVmean and FDG SUVmean were significantly correlated with body weight, BMI, leptin, and sclerostin levels (p &lt; 0.05). NaF SUVmean was significantly positively correlated with BMI and leptin for both the hip and SI joints (p &lt; 0.05). No significant correlation was observed between either PET parameter and age, height, erythrocyte sedimentation rate (ESR), and interleukins 1 and 6 (IL-1 and IL-6); however, FDG was correlated with inflammatory markers such as C-reactive protein (CRP) and patient global visual analogue scale (VAS-PtGlobal) in some joints. In this study, both FDG and NaF uptake were quantified in large joints of patients with RA using CT segmentation. NaF and FDG SUVmean were correlated with clinical variables related to body weight and adiposity, suggesting that degenerative joint disease may play a larger role in influencing the uptake of these tracers in large joints than RA disease activity. FDG and its correlation with markers of inflammation such as CRP and VAS-PtGlobal suggests that this tracer may serve as a more specific marker for RA disease activity than NaF. Larger prospective and longitudinal data are necessary to gain a better understanding of the roles of FDG and NaF in evaluating RA joint activity in these joints.

• Subtirelu, Robert Christopher; Teichner, Eric Michael; Su, Yvonne; Al-Daoud, Omar; Patel, Milan & Patil, Shiv [Show all 11 contributors for this article] (2023). Aging and Cerebral Glucose Metabolism: ¹⁸F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients. Life. 13(10). doi: 10.3390/life13102044. Full text in Research Archive Show summary

  Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.

• Kvassheim, Monika; Tornes, Anna Julie Kjøl; Juzenienne, Asta; Stokke, Caroline & Rootwelt-Revheim, Mona Elisabeth (2023). Imaging of 212Pb in mice with a clinical SPECT/CT. EJNMMI Physics. ISSN 2197-7364. 10(1), p. 1–11. doi: 10.1186/s40658-023-00571-6. Full text in Research Archive
• Grønningsæter, Simen Rykkje; Blakkisrud, Johan; Selboe, Silje; Rootwelt-Revheim, Mona Elisabeth; Bruland, Øyvind & Bønsdorff, Tina Bjørnlund [Show all 8 contributors for this article] (2023). Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis. Frontiers in Medicine. 10, p. 1–10. doi: 10.3389/fmed.2023.1058914. Full text in Research Archive Show summary

  Aim Two ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles ( 224 Ra-CaCO 3 -MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public. Method Six patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of 224 Ra-CaCO 3 -MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of 224 Ra-CaCO 3 -MP, to estimate the activity concentration of 224 Ra and 212 Pb. Results The patients’ median effective whole-body half-life of 224 Ra-CaCO 3 -MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9–6.8 μSv per patient, and daily contact resulted in 4.3–31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7–83.0 μSv. The highest activity concentrations of 224 Ra and 212 Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for 224 Ra and 628 Bq/g for 212 Pb. Conclusion The number of patients treated with 224 Ra-CaCO 3 -MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200–400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.

• Puri, Tanuj; Frost, Michelle L.; Moore, Amelia E. B.; Choudhury, Ananya; Vinjamuri, Sobhan & Mahajan, Abhishek [Show all 17 contributors for this article] (2023). Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications. Frontiers in Endocrinology. 14. doi: 10.3389/fendo.2023.1236881. Full text in Research Archive Show summary

  We review the rationale, methodology, and clinical utility of quantitative [ 18 F] sodium fluoride ([ 18 F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (K i , also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [ 18 F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [ 18 F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique.

• Jenul, Anna Selina; Stokmo, Henning Langen; Schrunner, Stefan; Hjortland, Geir Olav; Rootwelt-Revheim, Mona Elisabeth & Tomic, Oliver (2023). Towards Understanding the Survival of Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms: An Investigation of Ensemble Feature Selection in the Prediction of Overall Survival. arXiv.org. ISSN 2331-8422. doi: 10.48550/arXiv.2302.10106. Full text in Research Archive Show summary

  Determining the most informative features for predicting the overall survival of patients diagnosed with high-grade gastroenteropancreatic neuroendocrine neoplasms is crucial to improve individual treatment plans for patients, as well as the biological understanding of the disease. Recently developed ensemble feature selectors like the Repeated Elastic Net Technique for Feature Selection (RENT) and the User-Guided Bayesian Framework for Feature Selection (UBayFS) allow the user to identify such features in datasets with low sample sizes. While RENT is purely data-driven, UBayFS is capable of integrating expert knowledge a priori in the feature selection process. In this work we compare both feature selectors on a dataset comprising of 63 patients and 134 features from multiple sources, including basic patient characteristics, baseline blood values, tumor histology, imaging, and treatment information. Our experiments involve data-driven and expert-driven setups, as well as combinations of both. We use findings from clinical literature as a source of expert knowledge. Our results demonstrate that both feature selectors allow accurate predictions, and that expert knowledge has a stabilizing effect on the feature set, while the impact on predictive performance is limited. The features WHO Performance Status, Albumin, Platelets, Ki-67, Tumor Morphology, Total MTV, Total TLG, and SUVmax are the most stable and predictive features in our study.

• Ayubcha, Cyrus; Rigney, Grant; Uy, Genevieve; Mirbod, Melika; Rootwelt-Revheim, Mona-Elisabeth & Werner, Thomas J. [Show all 7 contributors for this article] (2023). Radiotracers, Positron Emission Tomography Imaging and Traumatic Brain Injury. In Rajendram, Rajkumar; Preedy, Victor R. & Patel, Vinood B. (Ed.), Biomarkers in Trauma, Injury and Critical Care. Springer Nature. ISSN 9783031073953. p. 323–343. doi: 10.1007/978-3-031-07395-3_15. Full text in Research Archive
• Dahlberg, Daniel; Holm, Sverre; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Stensland, Maria & Souza, Gustavo Antonio De [Show all 11 contributors for this article] (2023). Bacterial Brain Abscesses Expand Despite Effective AntibioticTreatment: A Process Powered by Osmosis Due to NeutrophilCell Death. Neurosurgery. ISSN 0148-396X. doi: 10.1227/neu.0000000000002792. Full text in Research Archive Show summary

  BACKGROUND AND OBJECTIVES: A bacterial brain abscess is an emergency and should be drained of pus within24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pusdrainage entails brain abscess expansion and what the underlying mechanism might be.METHODS: Repeated brain MRI of 47 patients who did not undergo immediate pus drainage, pus osmolarity measurements, immunocytochemistry, proteomics, and 18F-fluorodeoxyglucose positron emission tomography.RESULTS: Time from first to last MRI before neurosurgery was 1 to 14 days. Abscesses expanded in all but 2 patients: Themedian average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even ifthe pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to behyperosmolar (median value 360 mOsm; range 266-497; n = 14; normal cerebrospinal fluid osmolarity is ∼290 mOsm).Hyperosmolarity would draw water into the abscess cavity, causing abscess expansion in a ballooning manner throughincreased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment ofneutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and othermacromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases,citrullinated histone, myeloperoxidase, elastase, cathelicidin). Previous studies have shown very high levels of osmolytes(ammonia, amino acids) in brain abscess pus. 18F-fluorodeoxyglucose positron emission tomography showed focalneocortical hypometabolism 1 to 8 years after brain abscess, indicating long-lasting damage to brain tissue.CONCLUSION: Brain abscesses expand despite effective antibiotic treatment. Furthermore, brain abscesses cause lastingdamage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.

• Stenberg, Vilde Yuli; Tornes, Anna Julie Kjøl; Nilsen, Hogne Røed; Rootwelt-Revheim, Mona Elisabeth; Bruland, Øyvind & Larsen, Roy Hartvig [Show all 7 contributors for this article] (2022). Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001. Cancers. 14(11). doi: 10.3390/cancers14112784. Full text in Research Archive Show summary

  This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

• Zadeh, Mahdi Zirakchian; Asadollahi, Shadi; Kaghazchi, Fatemeh; Raynor, William Y.; Seraj, Siavash Mehdizadeh & Werner, Thomas J. [Show all 11 contributors for this article] (2022). Prognostic significance of conventional and volumetric PET parameters with and without partial volume correction in the assessment of head and neck squamous cell carcinoma. Nuclear medicine communications. ISSN 0143-3636. 43(7), p. 800–806. doi: 10.1097/MNM.0000000000001573. Full text in Research Archive
• Maggadottir, Solrun Melkorka; Kvalheim, Gunnar; Wernhoff, Patrik; Sæbøe-Larssen, Stein; Rootwelt-Revheim, Mona Elisabeth & Josefsen, Dag [Show all 9 contributors for this article] (2022). A phase I/II escalation trial design T-RAD: Treatment of metastatic lung cancer with mRNA-engineered T cells expressing a T cell receptor targeting human telomerase reverse transcriptase (hTERT). Frontiers in Oncology. 12, p. 1–14. doi: 10.3389/fonc.2022.1031232. Full text in Research Archive Show summary

  Background Adoptive cellular therapy (ACT) with genetically modified T cells aims to redirect T cells against resistant cancers through introduction of a T cell receptor (TCR). The Radium-4 TCR was isolated from a responding patient in a cancer vaccination study and recognizes the enzymatic component of human Telomerase Reverse Transcriptase (hTERT) presented on MHC class II (HLA-DP04). hTERT is a constitutively overexpressed tumor-associated antigen present in most human cancers, including non-small-cell lung cancer (NSCLC), which is the second most common type of cancer worldwide. Treatment alternatives for relapsing NSCLC are limited and survival is poor. To improve patient outcome we designed a TCR-based ACT study targeting hTERT. Methods T-RAD is a phase I/II study to evaluate the safety and efficacy of Radium-4 mRNA electroporated autologous T cells in the treatment of metastatic NSCLC with no other treatment option. Transient TCR expression is applied for safety considerations. Participants receive two intravenous injections with escalating doses of redirected T cells weekly for 6 consecutive weeks. Primary objectives are safety and tolerability. Secondary objectives include progression-free survival, time to progression, overall survival, patient reported outcomes and overall radiological response. Discussion Treatment for metastatic NSCLC is scarce and new personalized treatment options are in high demand. hTERT is a tumor target applicable to numerous cancer types. This proof-of-concept study will explore for the first time the safety and efficacy of TCR mRNA electroporated autologous T cells targeting hTERT. The T-RAD study will thus evaluate an attractive candidate for future immunotherapy of solid tumors.

• Bassir, Ali; Raynor, William Y.; Park, Peter Sang Uk; Werner, Thomas J.; Alavi, Abass & Rootwelt-Revheim, Mona Elisabeth (2022). Molecular imaging in atherosclerosis. Clinical and translational imaging. ISSN 2281-5872. 10, p. 259–272. doi: 10.1007/s40336-022-00483-y. Full text in Research Archive Show summary

  Purpose As atherosclerosis is a prominent cause of morbidity and mortality, early detection of atherosclerotic plaques is vital to prevent complications. Imaging plays a significant role in this goal. Molecular imaging and structural imaging detect different phases of atherosclerotic progression. In this review, we explain the relation between these types of imaging with the physiopathology of plaques, along with their advantages and disadvantages. We also discuss in detail the most commonly used positron emission tomography (PET) radiotracers for atherosclerosis imaging. Method A comprehensive search was conducted to extract articles related to imaging of atherosclerosis in PubMed, Google Scholar, and Web of Science. The obtained papers were reviewed regarding precise relation with our topic. Among the search keywords utilized were "atherosclerosis imaging", "atherosclerosis structural imaging", "atherosclerosis CT scan" "positron emission tomography", "PET imaging", "18F-NaF", "18F-FDG", and "atherosclerosis calcification." Result Although structural imaging such as computed tomography (CT) offers essential information regarding plaque structure and morphologic features, these modalities can only detect macroscopic alterations that occur later in the disease’s progression, when the changes are frequently irreversible. Molecular imaging modalities like PET, on the other hand, have the advantage of detecting microscopic changes and allow us to treat these plaques before irreversible changes occur. The two most commonly used tracers in PET imaging of atherosclerosis are 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG). While there are limitations in the use of 18F-FDG for the detection of atherosclerosis in coronary arteries due to physiological uptake in myocardium and high luminal blood pool activity of 18F-FDG, 18F-NaF PET is less affected and can be utilized to analyze the coronary arteries in addition to the peripheral vasculature. Conclusion Molecular imaging with PET/CT has become a useful tool in the early detection of atherosclerosis. 18F-NaF PET/CT shows promise in the early global assessment of atherosclerosis, but further prospective studies are needed to confirm its role in this area.

• Kvassheim, Monika; Rootwelt-Revheim, Mona Elisabeth & Stokke, Caroline (2022). Quantitative SPECT/CT imaging of lead-212: a phantom study. EJNMMI Physics. ISSN 2197-7364. 9(1). doi: 10.1186/s40658-022-00481-z. Full text in Research Archive Show summary

  Background Lead-212 (212Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (212Bi) via β-particle emission. This extends the problematic short half-life of 212Bi. In preparation for upcoming clinical trials with 212Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of 212Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation. Results Both acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16–21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter. Conclusions Only minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of 212Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

• Alavi, Abass; Werner, Thomas J.; Høilund-Carlsen, Poul Flemming. & Rootwelt-Revheim, Mona Elisabeth (2022). Can Target-to-Background Ratio Measurement Lead to Detection and Accurate Quantification of Atherosclerosis With FDG PET? Likely Not. Clinical Nuclear Medicine. ISSN 0363-9762. 47(6), p. 532–536. doi: 10.1097/RLU.0000000000004131. Full text in Research Archive
• Stokke, Caroline; Nørgaard, Jakob Nordberg; Phillips, Hilde Feiring; Sherwani, Alexander Gul; Nuruddin, Syed Mohammad & Connelly, James Pattrick [Show all 8 contributors for this article] (2022). Comparison of [18F]fluciclovine and [18F]FDG PET/CT in Newly Diagnosed Multiple Myeloma Patients. Molecular Imaging and Biology. ISSN 1536-1632. 24(5), p. 842–851. doi: 10.1007/s11307-022-01734-0. Full text in Research Archive Show summary

  Abstract Purpose [ 18 F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [ 18 F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [ 18 F]fluciclovine PET compared to [ 18 F]FDG PET in newly diagnosed MM patients. Procedures Thirteen newly diagnosed transplant eligible MM patients were imaged both with [ 18 F]FDG PET/CT and [ 18 F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUV max of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUV max by blood or bone marrow SUV max . Between-group differences and correlations were assessed with paired t -tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples. Results Nine subjects were assessed positively by [ 18 F]FDG PET (69%) and 12 positives by [ 18 F]fluciclovine PET (92%). All positive subjects had [ 18 F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [ 18 F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [ 18 F]fluciclovine PET had fewer or no visible lesions on [ 18 F]FDG PET. The mean lesion SUV max values were 8.2 and 3.8 for [ 18 F]fluciclovine and [ 18 F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [ 18 F]fluciclovine and [ 18 F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [ 18 F]fluciclovine and [ 18 F]FDG. The lesion SUV max and ratios were significantly higher for [ 18 F]fluciclovine (all p  &lt; 0.01). Local [ 18 F]fluciclovine SUV max or SUV mean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated ( p  = 0.048). There were no significant correlations between [ 18 F]FDG SUVs and plasma cells ( p  = 0.82). Conclusions Based on this pilot study, [ 18 F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [ 18 F]fluciclovine PET/CT can out-perform [ 18 F]FDG PET/CT at diagnosis.

• Raynor, William Y.; Borja, Austin J.; Zhang, Vincent; Kothekar, Esha; Lau, Hui Chong & Ng, Sze Jia [Show all 14 contributors for this article] (2022). Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography. PET Clinics. ISSN 1556-8598. 17(4), p. 653–659. doi: 10.1016/j.cpet.2022.07.009. Full text in Research Archive
• Helgebostad, Rasmus; Rootwelt-Revheim, Mona Elisabeth; Johnsrud, Kjersti; Amlie, Kristine; Alavi, Abass & Connelly, James Pattrick (2022). Clinical Applications of Somatostatin Receptor (Agonist) PET Tracers beyond Neuroendocrine Tumors. Diagnostics (Basel). 12(2), p. 1–19. doi: 10.3390/diagnostics12020528. Full text in Research Archive Show summary

  Somatostatin receptor (SSTR) agonist tracers used in nuclear medicine scans are classically used for neuroendocrine tumor diagnosis and staging. SSTR are however, expressed more widely in a variety of cells as seen in the distribution of physiological tracer uptake during whole body scans. This provides opportunities for using these tracers for applications other than NETs and meningiomas. In this qualitative systematic review, novel diagnostics in SSTR-PET imaging are reviewed. A total of 70 studies comprised of 543 patients were qualitatively reviewed. Sarcoidosis, atherosclerosis and phosphaturic mesenchymal tumors represent the most studied applications currently with promising results. Other applications remain in progress where there are many case reports but a relative dearth of cohort studies. [18F]FDG PET provides the main comparative method in many cases but represents a well-established general PET technique that may be difficult to replace, without prospective clinical studies.

• Park, Peter Sang Uk; Raynor, William Y.; Khurana, Navpreet; Sun, Yusha; Werner, Thomas J. & Høilund-Carlsen, Poul Flemming [Show all 8 contributors for this article] (2022). Application of 18F-NaF-PET/CT in assessing age-related changes in the cervical spine. Quantitative Imaging in Medicine and Surgery (QIMS). ISSN 2223-4292. 12(6), p. 3314–3324. doi: 10.21037/qims-21-1174. Full text in Research Archive Show summary

  Background: Cervical spondylosis is the degeneration of cervical spine often associated with aging and neck pain. As the degenerative changes are coupled with altered osteoblastic activity, imaging modalities sensitive to such molecular changes could be valuable for clinical assessment, disease prophylaxis, and monitoring early therapy response. In this study, we examined the role of 18F-sodium fluoride-positron emission tomography/computed tomography (18F-NaF-PET/CT) in detecting age-associated changes in the cervical spine of an adult population with broad age spectrum. Methods: In this retrospective cross-sectional study, we analyzed 18F-NaF-PET/CT scans of 88 control volunteers (43 females, 45 males) with age ranging from 21 to 75 years (mean =44.6, standard deviation, 14.0) divided into younger (21–45 years) and older (46–75 years) age groups. A semi-automated global assessment technique was used to measure 18F-NaF uptake in C2-C4 and C5-C7 vertebrae of the subjects. Furthermore, a CT-based scoring system was devised to measure the degree of structural degeneration. Results: There was a significant difference in 18F-NaF uptake of the younger and older groups at the C5-C7 vertebrae for both females (younger: mean =4.13, 95% CI: 3.72–4.55; older: mean = 4.80, 95% CI: 4.40–5.20; P=0.005) and males (younger: mean =3.66, 95% CI: 3.24–4.09; older: mean =4.22, 95% CI: 3.80–4.64; P=0.009), but not at the C2-C4 vertebrae. Furthermore, there was a positive correlation between the degree of degeneration and 18F-NaF uptake at both C2-C4 and C5-C7 spinal segments of both sexes. Conclusions: Aging is associated with increased 18F-NaF uptake in the cervical spine, which may be associated with osteoblastic activity coupled with degeneration. Our study alludes to the potential role of 18F-NaF-PET/CT in evaluating age-related degeneration and osteoarthritis of the spine. Keywords: Positron emission tomography/computed tomography (PET/CT); sodium fluoride; aging; cervical spine; cervical spondylosis

• Tornes, Anna Julie Kjøl; Stenberg, Vilde Yuli; Bruland, Øyvind; Rootwelt-Revheim, Mona Elisabeth; Larsen, Roy H & Juzenienne, Asta (2022). Targeted alpha therapy with the 224Ra/212Pb-TCMC-TP-3 dual alpha solution in a multicellular tumor spheroid model of osteosarcoma. Frontiers in Medicine. 9. doi: 10.3389/fmed.2022.1058863. Full text in Research Archive Show summary

  Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression. We propose a novel dual alpha targeting solution containing two radionuclides from the same decay chain, including the bone-seeking 224 Ra, and cancer cell-surface seeking 212 Pb-TCMC-TP-3 for the treatment of osteoblastic bone cancers, circulating cancer cells and micrometastases. In this in vitro study, the cytotoxic effects of 212 Pb-TCMC-TP-3 (single alpha solution) and 224 Ra/ 212 Pb-TCMC-TP-3 (dual alpha solution) were investigated in a multicellular spheroid model mimicking micrometastatic disease in osteosarcoma. OHS spheroids with diameters of 253 ± 98 μm treated with 4.5, 2.7, and 3.3 kBq/ml of 212 Pb-TCMC-TP-3 for 1, 4, and 24 h, respectively, were disintegrated within 3 weeks. The 212 Pb-TCMC-TP-3 induced a 7-fold delay in spheroid doubling time compared to a 28-times higher dose with the non-specific 212 Pb-TCMC-rituximab. The 224 Ra/ 212 Pb-TCMC-TP-3 completely disintegrated spheroids with diameters of 218–476 μm within 3 and 2 weeks after 4 and 24 h incubation with 5 kBq/ml, respectively. Treatment with 1 kBq/ml of 224 Ra/ 212 Pb-TCMC-TP-3 for 24 h caused an 11.4-fold reduction in spheroid viability compared with unconjugated 224 Ra/ 212 Pb. The single and dual alpha solutions with TP-3 showed cytotoxicity in spheroids of clinically relevant size, which warrant further testing of the dual alpha solution using in vivo osteosarcoma models.

• Løndalen, Ayca; Blakkisrud, Johan; Rootwelt-Revheim, Mona Elisabeth; Dahle, Jostein; Kolstad, Arne & Stokke, Caroline (2022). FDG PET/CT and Dosimetric Studies of 177Lu-Lilotomab Satetraxetan in a First-in-Human Trial for Relapsed Indolent non-Hodgkin Lymphoma—Are We Hitting the Target? Molecular Imaging and Biology. ISSN 1536-1632. p. 807–817. doi: 10.1007/s11307-022-01731-3. Full text in Research Archive Show summary

  Abstract Purpose [ 177 Lu]Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed indolent non-Hodgkin lymphoma. In this study, new methods were assessed to calculate the mean absorbed dose to the total tumor volume, with the aim of establishing potential dose–response relationships based on 2-deoxy-2-[18F]fluoro- d -glucose (FDG) positron emission tomography (PET) parameters and clinical response. Our second aim was to study if higher total tumor burden induces reduction in the 177 Lu-lilotomab satetraxetan accumulation in tumor. Procedures Fifteen patients with different pre-dosing (non-radioactive lilotomab) regimens were included and the cohort was divided into low and high non-radioactive lilotomab pre-dosing groups for some of the analyses. 177 Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15, or 20 MBq/kg. Mean absorbed doses to the total tumor volume ( tTAD ) were calculated from posttreatment single-photon emission tomography (SPECT)/computed tomography (CT) acquisitions. Total values of metabolic tumor volume ( tMTV ), total lesion glycolysis ( tTLG ) and the percent change in these parameters were calculated from FDG PET/CT performed at baseline, and at 3 and 6 months after RIT. Clinical responses were evaluated at 6 months as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). Results Significant decreases in tMTV and tTLG were observed at 3 months for patients receiving tTAD  ≥ 200 cGy compared to patients receiving tTAD  &lt; 200 cGy ( p  = .03 for both). All non-responders had tTAD  &lt; 200 cGy. Large variations in tTAD were observed in responders. Reduction in 177 Lu-lilotomab satetraxetan uptake in tumor volume was not observed in patients with higher baseline tumor burden (tTMV). Conclusion tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm 3 ) did not induce reduction in radioimmunoconjugate accumulation in tumor.

• Høilund-Carlsen, Poul F.; Piri, Reza; Madsen, Per Lav; Rootwelt-Revheim, Mona Elisabeth; Werner, Thomas J. & Alavi, Abass [Show all 8 contributors for this article] (2022). Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging. International Journal of Molecular Sciences. ISSN 1661-6596. 23(18). doi: 10.3390/ijms231810268. Full text in Research Archive Show summary

  Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

• Stokmo, Henning Langen; Aly, Mahmoud; Lothe, Inger Marie Bowitz; Borja, Austin J.; Seraj, Siavash Mehdizadeh & Ghorpade, Rina [Show all 13 contributors for this article] (2022). Volumetric parameters from [18F]FDG PET/CT predicts survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms. Journal of Neuroendocrinology (JNE). ISSN 0953-8194. 34(7). doi: 10.1111/jne.13170. Full text in Research Archive Show summary

  A positive fluorine-18 labelled 2-deoxy-2-fluoroglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has been associated with more aggressive disease and less differentiated neuroendocrine neoplasms (NEN). Although a high maximum standardized uptake value (SUVmax) predicts poor outcome in NEN, volumetric parameters from [18F]FDG PET have not been evaluated for prognostication in a pure high-grade gastroenteropancreatic (GEP) NEN cohort. In this retrospective observational study, we evaluated the volumetric PET parameters total metabolic tumour volume (tMTV) and total total lesion glycolysis (tTLG) for independent prognostication of overall survival (OS). High-grade GEP NEN patients with [18F]FDG PET/CT examination and biopsy within 90 days were included. Total MTV and tTLG were calculated using an adaptive thresholding software. Patients were dichotomised into low and high metabolic groups based on median tMTV and tTLG. OS was compared using Kaplan–Meier estimator and log-rank test. Uni and multivariable Cox regression was used to estimate effect sizes and adjust for tumour differentiation and SUVmax. Sixty-six patients (median age 64 years) were included with 14 NET G3 and 52 NEC cases after histological re-evaluation. Median tMTV was 208 cm3 and median tTLG 1899 g. Median OS in the low versus high tMTV-group was 21.2 versus 5.7 months (HR 2.53, p = 0.0007) and 22.8 versus 5.7 months (HR 2.42, p = 0.0012) in the tTLG-group. Adjusted for tumour differentiation and SUVmax, tMTV and tTLG still predicted for poor OS, and both tMTV and tTLG were stronger prognostic parameters than SUVmax. Both regression models showed a strong association between volumetric parameters and OS for both neuroendocrine tumours (NET) G3 and neuroendocrine carcinomas (NEC). OS for the tTLG low metabolic NEC was much higher than for the tTLG high metabolic NET G3 (18.3 vs. 5.7 months). High-grade GEP NEN patients with high tMTV or tTLG had a worse OS regardless of tumour differentiation (NET G3 or NEC). Volumetric PET parameters were stronger prognostic parameters than SUVmax.

• Koa, Benjamin; Raynor, William Y.; Park, Peter Sang Uk; Borja, Austin J.; Singhal, Sachi & Kuang, Angie [Show all 10 contributors for this article] (2022). Feasibility of Global Assessment of Bone Metastases in Prostate Cancer with 18F-Sodium Fluoride-PET/Computed Tomography. PET Clinics. ISSN 1556-8598. 17(4), p. 631–640. doi: 10.1016/j.cpet.2022.07.007. Full text in Research Archive
• Borja, Austin J.; Saini, Jitender; Raynor, William Y.; Ayubcha, Cyrus; Werner, Thomas J. & Alavi, Abass [Show all 8 contributors for this article] (2022). Role of Molecular Imaging with PET/MR Imaging in the Diagnosis and Management of Brain Tumors. PET Clinics. ISSN 1556-8598. 17(3), p. 431–451. doi: 10.1016/j.cpet.2022.03.002. Full text in Research Archive
• Raynor, William Y.; Borja, Austin J.; Hancin, Emily C.; Werner, Thomas J.; Alavi, Abass & Rootwelt-Revheim, Mona-Elisabeth (2021). Novel musculoskeletal and orthopedic applications of 18F-sodium fluoride PET. PET Clinics. ISSN 1556-8598. 16(2), p. 295–311. doi: 10.1016/j.cpet.2020.12.006. Full text in Research Archive Show summary

  Key points 18F-sodium fluoride (NaF) PET can detect causes of bone pain and traumatic injuries that cannot be successfully visualized by other modalities such as radiography, bone scintigraphy, computed tomography, and magnetic resonance. Thus, NaF-PET may contribute to the assessment of occult fractures, child abuse, and stress-related injuries. NaF-PET is an excellent modality to assess osteoarthritis, ankylosing spondylitis, and temporomandibular joint dysfunction. More studies are needed to determine its potential role in inflammatory arthropathies such as rheumatoid arthritis and psoriatic arthritis. Complications of orthopedic surgery such as hardware loosening and infection are readily visualized by NaF-PET. Heterotopic ossification after surgery is another possible imaging target that requires further exploration. Metabolic bone diseases such as osteoporosis and Paget disease can be evaluated over time with NaF-PET to determine effects of pharmacologic interventions such as bisphosphonates and teriparatide. NaF-PET may have a role in assessing primary bone tumors such as osteosarcoma, helping to determine response to treatment and guiding patient management decisions.

• Koa, Benjamin; Borja, Austin J.; Aly, Mahmoud; Padmanabhan, Sayuri; Tran, Joseph & Zhang, Vincent [Show all 14 contributors for this article] (2021). Emerging role of 18F-FDG PET/CT in Castleman disease: a review. Insights into Imaging. 12, p. 1–11. doi: 10.1186/s13244-021-00963-1. Full text in Research Archive Show summary

  Castleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging. Trial registration ClinicalTrials.gov, NCT02817997, Registered 29 June 2016, https://clinicaltrials.gov/ct2/show/NCT02817997

• Ayubcha, Cyrus; Moghbel, Mateen; Borja, Austin J.; Newberg, Andrew; Werner, Thomas J. & Alavi, Abass [Show all 7 contributors for this article] (2021). Tau Imaging in Head Injury. PET Clinics. ISSN 1556-8598. 16(2), p. 249–260. doi: 10.1016/j.cpet.2020.12.009. Full text in Research Archive Show summary

  Key points Misfolded tau proteins underlie chronic traumatic encephalopathy (CTE) related to head trauma. Tau-PET radiotracers have shown superior specificity and selectivity. Tau-PET imaging of head trauma populations has shown elevated tau uptake related to CTE.

• Borja, Austin J.; Hancin, Emily C.; Raynor, William Y.; Ayubcha, Cyrus; Detchou, Donald K. & Werner, Thomas J. [Show all 8 contributors for this article] (2021). A critical review of PET tracers used for brain tumor imaging. PET Clinics. ISSN 1556-8598. 16(2), p. 219–231. doi: 10.1016/j.cpet.2020.12.004. Full text in Research Archive Show summary

  Because enhancement on computed tomography (CT) and MR reflects blood-brain barrier (BBB) changes, molecular imaging with PET-based techniques is needed to assess brain tumor activity, especially in tumors with intact or partially intact BBB. 18F-fluorodeoxyglucose (FDG)-PET has been validated in tumor detection/delineation, recurrence, and prognostication. Although FDG remains the most widely used PET tracer in the evaluation of brain tumors, various other tracers, including amino acid indicators, have been studied extensively. Breakdown of the BBB plays a major role in visualizing brain tumors by radiolabeled amino acid tracers; therefore, this approach is suboptimal for assessing disease activity beyond CT and MR.

• Hancin, Emily C.; Raynor, William Y.; Borja, Austin J.; Werner, Thomas J.; Rootwelt-Revheim, Mona-Elisabeth & Alavi, Abass (2021). Non-18F-FDG/18F-NaF radiotracers proposed for the diagnosis and management of diseases of the heart and vasculature. PET Clinics. ISSN 1556-8598. 16(2), p. 273–284. doi: 10.1016/j.cpet.2020.12.005. Full text in Research Archive Show summary

  18F-FDG and 18F-NaF have been used extensively in the identification of various cardiovascular diseases, but not without limitations. Several other PET radiotracers have been identified as possible markers for cardiovascular-associated inflammation and infection. Non-18F-FDG/18F-NaF molecules may have utility as alternative radiotracers in the detection and management of cardiovascular diseases, but few have demonstrated clinical value.

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• Reinås, Karl Henrik Storhaug; Rootwelt-Revheim, Mona-Elisabeth; Fretheim, Håvard Halland; Johnsrud, Kjersti; Midtvedt, Øyvind & Sherwani, Alexander Gul [Show all 8 contributors for this article] (2026). Time is crucial: An Interaction analysis study of dilemmas between patients with inflammatory rheumatic diseases and health care professionals at a PET-CT facility. Annals of Rheumatic diseases. 34(2-4), p. 2387–2387. doi: https:/eular.sharepoint.com/sites/AbstractBookletPublication/Shared%20Documents/Forms/AllItems.aspx?id=%2Fsites%2FAbstractBookletPublication%2FShared%20Documents%2FEULAR%202026%20Abstract%20Book%20%28pre-Congress%29.pdf&parent=%2Fsites%2FAbstractBookletPublication%2FShared%20Documents&p=true&ga=1. Full text in Research Archive Show summary

  Background: Communication between health care professionals (HCP) and patients is essential in how to learn coping strategies for how to live satisfactorily with Inflammatory rheumatic diseases (IRDs). Communication act as a key resource for knowledge-sharing. It also supports a process of meaning-making, enabling both HCP and persons with IRDs to gain insights into the patients’ condition when the communication can occur in a safe, secure and trustful manner within the context of the health care sector. Person-centred care (PCC) emphasises that the relation between the HCP and patient should be in the form of a partnership, where the patients’ experiences are necessary to merge with the HCP’s professional training (evidence-based education) and clinical experience, to lay the best foundation for a fruitful collaboration that could benefit the tailor-made diagnosis and treatment trajectory. To facilitate an increase in health literacy (HL) for patients through communication, PCC could be useful, as one of several available intervention approaches. Even though PCC is implemented and known to various degrees, the principles are often used implicitly by showing empathy and concern for the patient’s condition and well-being. Oftentimes HCPs are facing communicative dilemmas for what to say and how to say it, to make their message as understandable and acceptable for the patient as possible, while avoiding misunderstandings that could prevent the communication to work properly. Preparation sessions for positron emission tomography and computer tomography (PET-CT), using fluorodeoxyglucose (FDG), are a health care setting that could make visible the challenges in implementing PCC for IRD patients under time-pressure. Time constraints are often present in the health care sector. As a result, time is crucial in shaping how HCPs are abled or constrained to help the patients to increase their HL. Objectives: Communicative dilemmas need to be resolved to ensure that patients receive the health care they need and get the knowledge required for conducting the PET-CT procedure. Such knowledge, combined with the rationale behind the procedure, also helps lay the foundation for the patients to understand on which conditions the image-taking and diagnostic information is based. To understand how HL could be increased in IRD-patients undergoing a preparation session for PET-CT, we asked: 1) In what way does the use of time in the health care encounter restrict or afford possibilities for learning? and 2) What communicative dilemmas do preparation sessions for PET-CT procedures entail? Methods: Fourteen patients (57.9±11.7 years, 9 women) with indications of IRDs (diagnosis=IgG4-related disease, sarcoidosis, spondyloarthritis, Kawasaki, unknown) and ten HCPs (31.2±5.5 years, 6 women) (7 radiographers and 3 biomedical scientists) taking part in a preparation session for a PET-CT scan at a large Norwegian hospital were videorecorded in November 2024-September 2025. A rheumatologist referred the IRD-patients to the study, whereupon they were called to confirm their interest in taking part in the study and later signed a written consent form before undergoing the procedure, as did the HCPs. Video recordings of the sessions were transcribed and analysed with interaction analysis (1), where the standardised structure of the interactional pattern was described and themes were identified through parts of the transcripts that thematized similar interaction sequences. Communicative dilemmas were used as an analytic lens, to investigate how the interaction sequences of interest were built up. Results: The interaction analysis identified four communicative dilemmas. 1) Informing about the time vs. overemphasising the duration, 2) Informing about the radioactive substance vs. provoking concerns, 3) Informing about the venous cannula insertion vs. making the venous cannula insertion too invasive and into focus, and 4) Timing the procedure accurately, adequately and correct vs. not be able to open for the experiences, concerns and small talk in the interaction. Balancing the emphasis between carrying out the medical procedure and explicitly recognizing the patient as an autonomous and capable individual was a significant challenge for HCPs, particularly when compounded by the constraints of limited time. The agency of the patient was shown through their initiation of asking questions and in how they followed up and responded to questions from the HCPs, while the HCPs differed in the degree to how much they deviated from the procedure’s checklist and added other kinds of information through their communication than they were required to from the standardised procedure and practice. Conclusions: Overall, we see that how to give precise, correct and enough information without worrying the patient unnecessary is a continuous challenge, that needs to be solved satisfactorily to help the patient cope with the situation and provide meaningful learning opportunities that could increase the HL for both patients and HCPs. The necessity to time the procedure, due to the radioactive substance and queue of patients, is a constraining factor in the context that limit the options for communication approaches that can be chosen and could sometimes make it harder to find satisfactory solutions for the communicative dilemmas the situation entails. However, it seems possible to provide information to patients that could improve the patients understanding of the procedure and the foundation for the diagnostic information through the images taken, despite time pressure, adapted to the needs and interests of the patients. Longitudinal studies could shed light on what IRD-patients have learned through the communication with HCPs in preparation sessions for PET-CT scans and how this could help living well and cope with the chronic disease. REFERENCES: [1] Jordan B, Henderson A. Interaction Analysis: Foundations and Practice. The Journal of the learning sciences. 1995;4(1):39–103. Acknowledgments: NIL. Disclosure of Interests: None declared. DOI: 10.1136/annrheumdis-2026-eular.C.29

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• Vikse, Jens; Haavardsholm, Erik; Lillejordet, Even; Aaløkken, Trond Mogens; Hammer, Hilde Berner & Diamantopoulos, Andreas P [Show all 8 contributors for this article] (2024). Bildeundersøkelser. In Vikse, Jens; Haavardsholm, Espen A. & Molberg, Øyvind (Ed.), Revmatologi. Universitetsforlaget. ISSN 9788215068589. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Alavi, Abass; Barrio, Jorge R.; Castellani, Rudolph J.; Costa, Tommaso & Herrup, Karl [Show all 13 contributors for this article] (2023). Revision of Alzheimer’s diagnostic criteria or relocation of the Potemkin village. Ageing Research Reviews. ISSN 1568-1637. 93. doi: 10.1016/j.arr.2023.102173. Full text in Research Archive
• Hoilund-Carlsen, Poul F.; Alavi, Abass & Rootwelt-Revheim, Mona Elisabeth (2023). Re: Aducanumab-Related ARIA: Paean or Lament? Clinical Nuclear Medicine. ISSN 0363-9762. 48(6), p. 505–506. doi: 10.1097/RLU.0000000000004509. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Rootwelt-Revheim, Mona Elisabeth; Alavi, Abass & Barrio, Jorge R. (2023). FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease. Clinical Nuclear Medicine. ISSN 0363-9762. 48(8), p. 689–691. doi: 10.1097/RLU.0000000000004710. Full text in Research Archive
• Haslerud, Torjan Magne & Rootwelt-Revheim, Mona Elisabeth (2023). Terapi + diagnostikk = teranostikk. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(1). doi: 10.4045/tidsskr.22.0776. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Werner, Thomas J.; Alavi, Abass & Rootwelt-Revheim, Mona Elisabeth (2022). Aducanumab-Related Amyloid-Related Imaging Abnormalities: Paean or Lament? Clinical Nuclear Medicine. ISSN 0363-9762. 47(7), p. 625–626. doi: 10.1097/RLU.0000000000004250. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Rootwelt-Revheim, Mona Elisabeth; Alavi, Abass; Satyamurthy, Nagichettiar & Barrio, Jorge R. (2022). Amyloid PET: A Questionable Single Primary Surrogate Efficacy Measure on Alzheimer Immunotherapy Trials. Journal of Alzheimer's Disease. ISSN 1387-2877. 90(4), p. 1395–1399. doi: 10.3233/JAD-220841. Full text in Research Archive
• Høilund-Carlsen, Poul F.; Rootwelt-Revheim, Mona Elisabeth & Alavi, Abass (2022). Alzheimer's Disease at a Crossroad: Time to Part from Amyloid to More Promising Aspects - Atherosclerosis for a Start. Journal of Alzheimer's Disease. ISSN 1387-2877. 88(2), p. 455–458. doi: 10.3233/JAD-220190. Full text in Research Archive
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• Butt, Baddar Pervaiz; Stokmo, Henning Langen; Rootwelt-Revheim, Mona Elisabeth; Sørbye, Halfdan & Hjortland, Geir Olav (2021). Folfirinox in the treatment of advanced gastroenteropancreatic neuroendocrine carcinomas. Annals of Oncology. ISSN 0923-7534. 32(S5), p. 915–915. doi: 10.1016/j.annonc.2021.08.190. Full text in Research Archive

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