FAPI Global Outreach Program

Introduction: Fibroblast activation protein (FAP) is a type II transmembrane glycoprotein that has shown to be highly expressed in cancer associated fibroblasts (CAFs) in the tumor microenvironment of many malignancies. The FAPI (FAP inhibitor) family of compounds targeting FAP have demonstrated ideal biodistribution and specificity as radiolabeled products for PET imaging with over 4,000 patients imaged with FAPI products.

Methods: We have established the FAPI global outreach program enabling investigators to lead their own investigator-initiated studies with the FAPI family of compounds for diagnostic use. This is accomplished by providing sites with GMP grade precursor for synthesis of [⁶⁸Ga]FAPI-46 and/or [¹⁸F]FAPI-74, coupled with manufacturing technical support and regulatory assistance. The program includes 190 investigator-led studies across 113 academic sites in 38 countries. The studies span chemistry, preclinical and clinical research projects in various disease areas. This has enabled the creation of a robust network and database that includes study type, disease areas, and the number of patients under investigation for clinical studies. Participating academic sites complete a simple annual progress report that provides data on study progress, grants awarded, articles published, number of patients imaged, safety reporting, and feedback on how to improve the program.

Results: Based on the latest data from the global outreach program, [⁶⁸Ga]FAPI-46 comprises 65% and [¹⁸F]FAPI-74 comprises 35% of the research conducted with FAPI compounds. The majority of studies are clinical studies at 65%, followed by pre-clinical at 24% and chemistry at 11%. The highest number of institutions in our program conducting FAPI research are in Germany with 30 institutions followed by the United States at 20. Studies are planned or in progress with 6,580 patients in various disease areas, and to date 1,082 patients have been imaged. Oncology is the most common disease under investigation at 58%, followed by fibrosis at 13%, cardiovascular disease at 7%, inflammation at 2%, another 14% in other misc. category and 6% studies as disease independent. In 2022, investigators in this program published nine papers with 20 publications expected in the first half of 2023. Participating sites also obtained 11 grants from granting agencies. No serious adverse events have been reported based on work in progress with [⁶⁸Ga]FAPI-46 and [¹⁸F]FAPI-74.

Conclusions: The FAPI global outreach program has proven successful in providing access to numerous investigators studying the utility of [⁶⁸Ga]FAPI-46 and [¹⁸F]FAPI-74 in various disease models and areas of unmet need. This allows further exploration of FAPI’s utility as a promising diagnostic or companion diagnostic tool.