Novel FAP-Targeted Heptamethine Cyanines for NIRF Imaging Applications

Abstract

Fibroblast activation protein (FAP) is a pan-cancer target that is useful for imaging, ideally all epithelial cancers. This work aimed to develop, characterize, and validate two novel FAP-targeted probes for optical imaging, both in vitro and in vivo. IRDye800CW and FNIRTag heptamethine cyanines were conjugated to the NH precursor of the well-known FAP inhibitor FAPI-46, which is widely employed in nuclear medicine. In addition to synthesis, the dyes were characterized in terms of physicochemical properties, biodistribution, and imaging performances in a breast cancer tumor model. FAPI-FNIRTag showed a stronger fluorescence and higher photostability compared to FAPI-IRDye800CW. Notably, both compounds exhibited strong tumor accumulation in TUBO breast cancer-bearing mice 24 h postadministration, suggesting potential for further investigation as fluorescence-guided surgery (FGS) agents.