177Lu-FAPI-04 is the therapeutic analogue of the PET imaging agent 68Ga-FAPI-04 from the FAPI. It is a DOTA-coupled quinolone analogue radiotherapeutic based on a Fibroplast Activation Protein (FAP)-specific enzyme inhibitor (FAPI). The same molecule has already been labeled with 90Y.

FAPIs targets cancer-associated fibroblasts (CAFs), yielding images with similar or better quality compared with 18F-FDG-PET/CT among patients with cancer. Besides cancer, FAPIs may also be used for benign diseases such as fibroses, atherosclerosis, rheumatoid arthritis, sarcoidosis, etc.

First attempts to label the best molecules developed within this family with therapeutic radionuclides have proven successful. 68Ga-FAPI-04 was tested in two breast cancer patients and 90Y-FAPI-04 was used in one patient. First preclinical data with 64Cu-FAPI-04 and 225Ac-FAPI-04 generated in pancreatic xenograft mouse models were published in October 2019. Of 15 synthesized FAPIs, FAPI-04 was identified as the most promising tracer for clinical applications. Phase I studies are under preparation.

Target/Mechanism: Fibroblasts

Leading Emitter: beta electrons (β–)