Grant: Project Grant

Radioactive drugs, aka radiopharmaceuticals, are playing an increasing role in both the diagnosis and treatment of many cancers. Pairs of radiopharmaceuticals, one of which delivers a diagnostic isotope while the other delivers a therapeutic isotope to the same molecular target in a tumor have been coined theranostic pairs. Existing clinical theranostic pairs are chemically similar, but not identical molecules, meaning they may behave differently in the body. This may lead to suboptimal diagnosis and/or treatment of the disease and a lengthy approval process for both drugs. Moreover, theranostic drugs for several targets expressed in common cancer types have not yet reached the clinic due to their suboptimal pharmacologic properties. Our project aims to develop a new generation of theranostic pairs, coined radiotwins, that are chemically identical and capable of either diagnosing or treating specific types of cancer depending on the radioisotope they carry. These radiotwins will carry the radioisotope fluorine-18, which provides superior imaging resolution compared to the currently most-used diagnostic isotope gallium-68. Furthermore, the identical chemical structure of the diagnostic and therapeutic companions will expedite their clinical trials, review and approval by health regulatory authorities. We have synthesized several radiotwin candidates targeting gastrin-releasing peptide receptor (GRPR) commonly found in prostate, breast and other cancers. While they show promising results in cell cultures and mice, further structural modifications are needed to improve their pharmacological properties. Here we aim to synthesize up to 50 new GRPR-targeting radiotwins, evaluate them in a series of in vitro assays, advance the most promising to preclinical studies in mice and, eventually, to human studies. Thus, we aim to deliver efficacious theranostic drugs that will extend the life expectancy and quality of life of Canadians suffering from common forms of cancer.