Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Sture Lindegren, Sahlgrenska universitetssjukhuset, Sweden
- Second opponent: Head of Department Bogdan Malkowski, Oncology Centre, Poland
- Third member and chair of the evaluation committee: Professor Trine Bjøro, Faculty of Medicine, University of Oslo
Chair of the Defence
Associate Professor Kristina Lindemann, Faculty of Medicine, University of Oslo
Principal Supervisor
PhD Tina B. Bønsdorff, Oncoinvest AS
Summary
Radionuclide therapy utilizing an α-emitting radioisotope combined with a carrier compound is a promising therapeutic strategy to combat micrometastases in cancer patients. The purpose of the carrier is to deliver the radiation to the tumor site so that the cancer cells are irradiated, become damaged and eventually die. Treatment of microsized tumors with α-emitting radionuclides has several advantages. The short range of α-particles in tissue allows high energy to be deposited within a distance corresponding to the size of the micrometastases, resulting in efficient cell kill and limited exposure to adjacent tissues.
In this thesis, two types of radiolabeled carriers have been evaluated: An anti-CD146 monoclonal antibody, named OI-3, for cell-specific targeting following systemic administration and inorganic calcium carbonate microparticles for local treatment of cavitary cancers. Both carriers were able to maintain and transport their radioactive payload to the target site. The OI-3 antibody bound selectively to human osteosarcoma cell lines in vitro and was able to target CD146 expressing tumors after intravenous injection in mice. Calcium carbonate microparticles labeled with radium-224 retained its radioactive payload to a large extent in vivo, as the radioactivity mainly remained in the peritoneal cavity of mice after intraperitoneal injection. For therapeutic purposes, the potential of combining the carriers with radium-224 or its daughter lead-212, which both generate emission of α-particles, was explored. Radium-224 labeled calcium carbonate microparticles exhibited significant antitumor effect in two murine models of human ovarian cancer. In addition, a novel method for producing antibodies labeled with lead-212 was proposed and its feasibility established. Here, a solution of radium-224 was used directly for labeling, eliminating the need to prepare a pure solution of lead-212, which is a relatively cumbersome and time-consuming process.
Additional information
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