Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [F]-labeled glycopeptide-containing FAPI with [F]FAPI-42.

Purpose: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [ Ga]FAPI-04 and [F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [F]-labeled glycopeptide-containing FAPI tracer (named [F]FAPT) for PET imaging of FAP in cancers.

Methods: [F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [F]FAPT PET/CT.

Results: Preclinical and clinical studies showed specific binding of [F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [F]FAPI-42. The biodistribution of [F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers.

Conclusion: [F]FAPT is better PET tracer than [F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.