Exploring the effects of Radium-224 in ovarian cancer

This Industrial PhD project of Oncoinvent AS has been focused on non-clinical evaluation of therapeutic effects of radium-224 labeled calcium carbonate microparticles for treatment of ovarian cancer. The project has been conducted in collaboration with the Katholieke Universiteit Leuven, Belgium. In the scope of the development of radium-224 labeled calcium carbonate microparticles (Radspherin®), different types of microparticles as carriers for intraperitoneal treatment delivery have been evaluated in an immune competent ovarian cancer mouse model. The project was designed to characterize the effects in the mouse model on ascites development, survival as well as on immune factors. A further a goal of the IPhD project was evaluation of the effect of combinations of Radspherin® with standard chemotherapy in non-clinical models. The IPhD project has resulted in published research papers and in expansion of a research platform for non-clinical evaluation of radiopharmaceutical cancer therapies.

- Research data on drug product candidates for cancer treatment - Increased knowledge within the field of alpha emitting radionuclide therapies for cancer treatment - Increased knowledge on effects of carrier compoud for intraperitoneal treatment of peritoneal carcinomatosis - Publication in scientific peer reviewed journals - Presentation of project and results to the scientific community at meetings and conferences

Ovarian cancer is the fifth leading cause of cancer related deaths in women and is still considered the most lethal gynecological malignancy, with high-grade serous ovarian cancer (HGSOC, an epithelial subtype of ovarian cancer) being the most dominant subtype. A major problem in ovarian cancer patients is the late diagnosis in an advanced stage of the disease (FIGO stages III and IV) because of the lack of symptoms at earlier stages of the disease. Most of the time, ovarian cancer patients present with a widespread metastatic disease in the abdominal cavity. One of the major problems in these patients, is the chemotherapy-resistant residual micrometastatic disease that remains present in the abdomen after debulking surgery. Therefore, new treatment strategies specifically targeting this residual disease in the peritoneal cavity are strongly needed. A promising alternative treatment option is the intraperitoneal injection of alpha-emitting radionuclides. They are strongly cytotoxic for the tumor cells but they have a short penetration depth in normal tissues, so surrounding radiosensitive organs in the abdomen will be spared. This makes alpha-emitting radionuclides a perfect candidate for intracavitary radiation therapy. The goal of Oncoinvent AS is to develop novel product candidates for cancer therapy. The main activity is the development of drugs for delivery of radioactive payloads to tumor tissues. Oncoinvents lead product candidate, Radspherin®, is a new alpha-emitting radioactive microsphere designed for treatment of metastatic cancers in body cavities, such as ovarian cancer. There is a need for extensive research for improved knowledge of the mechanism of action of novel radiotherapies. The present project will be involved in research activities to expand the knowledge and expertise of a new alpha-emitting therapy.