177Lu-iPSMA-iGRP78

177Lu-iPSMA-iGRP78 is a novel heterodimeric radiopharmaceutical designed for the targeted treatment of castration-resistant prostate cancer (CRPC). Developed by researchers at institutions including the Instituto Nacional de Investigaciones Nucleares (ININ) in Mexico, the compound utilizes a bispecific approach by simultaneously targeting the prostate-specific membrane antigen (PSMA) and cell surface glucose-regulated protein 78 (GRP78). Structurally, it consists of a lutetium-177 radionuclide coordinated by a DOTA-HYNIC chelator, which links a PSMA inhibitor (based on the Lys(Nal)-NH-CO-NH-Glu sequence) and a GRP78 inhibitor peptide (sequence WIFPWIQL) via a 4-maleimidobutyric acid linker. By targeting GRP78—a chaperone protein often overexpressed on the surface of aggressive and radioresistant cancer cells—alongside PSMA, the radioligand achieves significantly enhanced internalization and higher cytosolic radiation delivery compared to monomeric PSMA-targeting agents. This dual-targeting strategy is intended to improve therapeutic efficacy and overcome resistance mechanisms in metastatic prostate cancer by delivering targeted beta radiation more efficiently into the cancer cell.

Other names

177Lu-DOTA-HYNIC-iPSMA-iGRP78[177Lu]Lu-DOTA-HYNIC-iPSMA-iGRP78Lutetium (177Lu) iPSMA-iGRP78