67Cu-FRIP2

67Cu-FRIP2 is a fibroblast activation protein (FAP)-targeted radiopharmaceutical developed by researchers at the University of California, San Francisco (UCSF) and licensed to Therapaint. It belongs to a class of agents called "restricted interaction peptides" (RIPs). The molecule consists of a DOTA chelator labeled with the therapeutic beta-emitting radioisotope copper-67 (67Cu), conjugated to a modular peptide containing three domains: an N-terminal membrane-binding domain (derived from the antimicrobial peptide Temporin L), a FAPα-specific cleavage sequence (HQGP-FWML), and a C-terminal masking peptide. In its intact state, the masking peptide prevents membrane binding. Upon cleavage by FAPα (which is highly expressed by cancer-associated fibroblasts in the tumor microenvironment), the masking peptide is released, allowing the membrane-binding domain to adopt a helical conformation and anchor the radioactive payload to nearby cell membranes. This "activation-and-trapping" mechanism enhances tumor retention of the therapeutic isotope. Preclinical studies in mouse models of FAP-expressing tumors (such as glioblastoma and prostate cancer) have demonstrated significant tumor growth delay and prolonged survival.

Other names

67Cu-DOTA-FRIP2copper Cu 67 FRIP2