Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Section Lead Julia Brosch-Lenz, University of Augsburg,
- Second opponent: Associate professor Michel Koole, KU Leuven,
- Third member and chair of the evaluation committee: Associate Professor Anselm Schulz, University of Oslo
Chair of the Defence
Associate professor James Patrick Connelly, University of Oslo
Principal Supervisor
Associate professor Caroline Stokke, University of Oslo
Summary
Several new targeted alpha therapies have been developed in the recent years, which use alpha radiation to kill cancer cells by molecular targeting. It is common for the radionuclides used to also emit some photons as part of their decay chains, which can facilitate imaging and activity measurements. Complex decay schemes and low count rates complicate all measurements, but valuable information may still be gained from exploring the opportunities granted by these photon emissions. The thesis aims to answer the research question: How can imaging and modelling predict biodistributions for targeted alpha therapies early in development?
The question was explored in two parts. The first part studied imaging of 212Pb by Monte Carlo simulations, phantom studies, and a clinical study to determine what information could be extracted to support development of targeted alpha therapies with 212Pb. The findings in Paper I-IV showed that useful results for tumour targeting and normal tissue uptake could be achieved. Our results also indicated potential for quantification of post-injection 212Pb images. We studied the influence of high energy gamma emissions of daughter 208Tl on the acquired energy windows, and the results suggested that there may be great potential for image improvement by optimised reconstruction algorithms.
The second part of the thesis addressed the modelling part of the research question. In Paper IV and Paper V, we adapted tissue time-activity curves, whole body clearance rates, and a compartmental model to predict biokinetic behaviour for two different targeting mechanisms with alpha emitters. We also modelled daughter redistribution for seven different decay chains relevant for targeted alpha therapies. From the results, we could compare different radionuclide therapies prior to and early in development. The kinetics and stability of the 212Pb-based treatment in blood was also analysed to better understand its in vivo behaviour.
Together, the imaging and modelling informed on biodistributions for potential future targeted alpha therapies. We gained insight into how physical characteristics of radionuclides and their daughters could affect the outcome of a treatment by modelling, and we gained knowledge from early clinical development that may help optimise future studies. Future development in hardware and software could greatly improve data quality and consequently also understanding of targeted alpha therapies. Yet, valuable information is obtainable with available technology with thoughtful data analysis.
Additional information
Contact the research support staff.