Grant: Project Grant

Kidney cancer is one of the most lethal cancers in Canada with low five-year survival rate. The most common kidney cancer is clear cell renal cell carcinoma (ccRCC). Treatment options for ccRCC are limited, and effective diagnostic and therapeutic agents are urgently needed. The most recognized markers of ccRCC are two proteins called carbonic anhydrase IX (CAIX) and prostate-specific membrane antigen (PSMA). CAIX is located on the ccRCC cancer cells and PSMA is present on the tumor blood vessels. Several diagnostic agents targeting CAIX or PSMA have been developed. These agents carry a radio-tag. Once injected into patients, these diagnostic agents gradually bind to their markers (CAIX or PSMA), and accumulate into ccRCC tumors. The radiation emitted from the radio-tag can be detected and used to locate ccRCC tumors. While suitable for diagnosis, these agents cannot be used for treatment. For therapy, these agents need to carry a different radio-tag which emits a more damaging radiation to kill cancer cells. In addition, the amount of radioactive therapeutic agents accumulated in tumors needs to be further enhanced to achieve a better treatment efficacy. For this proposed project, we will design radioactive pharmaceuticals (radiopharmaceuticals) which can simultaneously target both CAIX and PSMA. This can increase their chances of binding to targets (CAIX and PSMA) in ccRCC and enhance the overall amount of accumulation in tumors, leading to better detection sensitivity and treatment efficacy. We will design and synthesize the dual-targeting radiopharmaceuticals, and evaluate their ability to detect and treat ccRCC using mice with implanted human ccRCC tumors. The success of this project will generate promising PSMA/CAIX dual-targeting radiopharmaceuticals. These radiopharmaceuticals are expected to have better detection sensitivity and treatment efficacy over currently reported PSMA- or CAIX-targeting agents for the management of ccRCC.