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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Senior Researcher Emma Aneheim, The Sahlgrenska Academy at the University of Gothenburg, Sweden
- Second opponent: Principal Scientist Sofia Frost, Roche Pharma Research and Early Development, Roche Innovation Center Welwyn (Roche Products Ltd), UK
- Third member and chair of the evaluation committee: Professor II Jørgen Wesche, University of Oslo
Chair of the Defence
Associate Professor Kristina Lindemann, University of Oslo
Principal Supervisor
Asta Juzeniene, Senior Researcher, Group Leader, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital
Summary
Cancer metastasis may result in intracavitary diseases such as peritoneal carcinomatosis in patients with advanced ovarian or gastrointestinal cancers. Surgery and chemotherapy are currently the principal treatments. Unfortunately, the majority of patients relapse because of residual tumor nodules and micrometastases in the peritoneal cavity. There is a need for new treatments.
Intraperitoneal (i.p.) treatment with radionuclides that result in alpha particle emission has been suggested to eliminate these tumors. The tumor cells are killed by the highly energetic and short-ranged alpha particles. Radium-224 (224Ra) and its daughter nuclide lead-212
(212Pb) are potential candidates for this application. To maximize the radiation to tumors and minimize the radiation to healthy tissues and organs, carrier vehicles for the radionuclides are necessary–such as calcium carbonate (CaCO3) microparticles, which can be radiolabeled with 224Ra and 212Pb.
This work investigates new generations of 224Ra-CaCO3 particles and novel 212Pb-CaCO3 particles for the treatment of peritoneal carcinomatosis. Various stabilizing additives and CaCO3 particles with different properties (e.g., particle size and labeling method) were evaluated to optimize the particles. Studies in mice were performed to evaluate biodistribution and therapeutic efficacy.
The tested particle variants resulted in high retention of 224Ra and 212Pb on the CaCO3 particles and reduced accumulation of radionuclides in critical organs compared to i.p. administration of unbound radionuclides. Furthermore, the radiolabeled particles extended the survival of tumor-bearing mice compared to control animals.
A novel generator was developed for the easy and convenient production of 212Pb.
Clinical studies of 224Ra-CaCO3 particles are underway while the 212Pb-CaCO3 particles are still in the discovery phase.
Additional information
Contact the research support staff.