Copper-64 Radiopharmaceuticals for Theranostic Applications

Based on the interesting preliminary data on the application of 64CuCl2 radiopharmaceutical in human cancers for diagnosis and therapy, the working group is focused on thorough preclinical/clinical investigations of the radiopharmaceutical. For these investigations, the priority is to better understand, and exploit for diagnostic and therapeutic purposes and endogenous Cu transport mechanisms. Cancer models to be investigated include prostate cancer, glioblastoma, lymphoma, breast cancer and melanoma. The unique opportunity of 64Cu to target various human cancers such as prostate, glioblastoma and melanoma also offers the opportunity to study the in-vitro and in-vivo behaviour of 64CuCl2 in these disease models. We therefore proposed to also evaluate the Cu-trafficking mechanisms, microdosimetry, radiobiology, etc. in comparison to other existing therapeutic radiopharmaceuticals (where available). A high incidence of receptor expression in either early- or late-stage/metastatic cancers creates potential for development of new and innovative monovalent and bivalent 64Cu radioligands to tailor receptor-specific uptake, optimize localization in cancerous tissues, and minimize uptake in normal tissues to produce high-quality, high-contrast PET images for early diagnosis and staging of human cancers and atherosclerotic plaques. In addition, these agents offer the added opportunity to be used for targeted therapy due to ideal particle emissions for the three decay modes. In these research investigations, we propose usage of selected targeting vectors (mono- or bivalent) to be delivered to participating countries to perform in-vitro and in-vivo evaluation of agents. For example, based upon a thorough review of the literature, the focal points of this CRP are to be peptides (e.g. particularly GRPR targeting, integrin targeting, somatostatin receptor targeting, etc.) and small molecules (e.g. PSMA inhibitors), and antibodies. In view of previous research investigations from numerous research groups around the world, the participants proposed usage of NOTA- or sarcophagine-based complexing agents for further evaluations to conjugate the targeting vectors in order to complex and stabilize the 64Cu metal centre.