DEVELOPMENT OF PSMA-TARGETED RADIOPHARMACUTICALS FOR ROUTINE CLINICAL APPLICATIONS

Abstract

Prostate cancer (PCa) is regarded one of the most prevalent cancer diagnoses amongst men in the United States and worldwide. Moreover, PCa is the second leading cause of cancer deaths in America. Prostate specific membrane antigen (PSMA) has been recognized as a promising molecular target in the detection of PCa, which has led to the development of specific radiolabeled tracers for PCa imaging and radioligand therapy. Consequently, PSMA-targeted radiopharmaceuticals applications in molecular imaging have significantly grown in recent years, evidenced by the number of clinical studies published, and the recent U.S. Food and Drug Administration (FDA) approval of Gallium-68 labeled PSMA-11 (68Ga-PSMA-11), a positron emission tomography imaging agent for PSMA positive lesions in men with prostate cancer. In this study, the aim is to preclinically evaluate Copper-64 labeled PSMA-I&T (64Cu-PSMA-I&T), as a potential PSMA-targeted imaging agent for routine clinical applications. In vitro and in vivo biological evaluation studies will be conducted to assess the specificity and binding affinity of the radiotracer to target, as well as estimating the absorbed dose delivered to target organs via internal radiation dosimetry measurements. PSMA-I&T (for Imaging & Therapy) offers high potential as a PSMA- binding-inhibitor, and is considered one of the first theranostic tracers, as it can be radiolabeled with various radiometals for imaging or therapy of PCa. While 64Cu is a well- established clinically available PET isotope that can be produced in large batches by a cyclotron and has a relatively long half-life (12.7 hrs.), which is important to facilitate the accessibility to and overcome logistical burdens associated with the production and commercial distribution of medical radioisotopes.