FAP-Targeted Fluorescent Imaging Agents to Study Cancer-Associated Fibroblasts In Vivo.

Area of Science:

• Biomedical imaging
• Cancer biology
• Medicinal chemistry

Background:

• Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein alpha (FAP) are prevalent in tumor microenvironments.
• FAP is an emerging target for positron emission tomography (PET) cancer imaging.
• There is a need for well-validated fluorescent small molecule imaging agents for in vivo CAF studies.

Purpose of the Study:

• To synthesize and characterize novel fluorescent small molecule imaging agents targeting FAP.
• To evaluate the performance of these agents for in vivo CAF labeling in solid tumors.

Main Methods:

• Synthesis of a series of fluorescent FAP imaging agents based on a quinolone azide inhibitor scaffold.
• Characterization of the synthesized compounds.
• Evaluation of probe performance for topical and intravenous administration in preclinical models.

Main Results:

• Several novel FAP Targeting Fluorescent probes (FTFs) were successfully synthesized and characterized.
• Selected FTFs demonstrated excellent performance in labeling CAF populations in solid tumors.
• Effective labeling was achieved through both topical application and intravenous delivery.

Conclusions:

• The developed FTFs are effective tools for in vivo imaging of FAP-expressing CAFs.
• These probes can facilitate the study of CAF biology and therapeutic targeting in solid tumors.
• The findings support the potential of FTFs for advancing cancer research and diagnostics.