FAP expression in alpha cells of Langherhans insulae-implications for FAPI radiopharmaceuticals' use

Purpose: Radiopharmaceuticals targeting fibroblast activation protein (FAP) alpha are increasingly studied for diagnostic and therapeutic applications. We discovered FAP expression at immunohistochemistry (IHC) in the alpha cells of the Langerhans insulae of few patients. Therefore, we planned an investigation aimed at describing FAP expression in the pancreas and discussing the implications for radioligand applications. Methods: We retrospectively included 40 patients from 2 institutions (20 pts each) according to the following inclusion/exclusion criteria: (i) pathology proven pancreatic ductal adenocarcinoma and neuroendocrine tumors (NET), 10 pts per each group at each center; (ii) and availability of paraffin-embedded tissue; and (iii) clinical-pathological records. We performed IHC analysis and applied a semiquantitative visual scoring system (0, negative staining; 1, present in less than 30%; 2, present in more than 30% of the area). FAP expression was assessed according to histology-NET (n = 20) vs ductal adenocarcinoma (n = 20)-and to previous treatments within the adenocarcinoma group. The local ethics committee approved the study (No. INT 21/16, 28 January 2016). Results: The population consisted of 24 males and 16 females, with a median age of 68 and a range of 14-84 years; 8/20 adenocarcinoma patients received chemotherapy. In all the Langerhans insulae (40/40), pancreatic alpha cells were found to express FAP, with a score of 2. No difference was found among NET (20/20) and adenocarcinoma (20/20), nor according to neoadjuvant chemotherapy in the adenocarcinoma cohort (received or not received). Conclusion: Pancreatic Langerhans islet alpha cells normally express FAP. This is not expected to influence the diagnostic accuracy of FAP-targeting tracers. In the therapeutic setting, our results suggest the need to better elucidate FAPI radioligands' effects on the Langerhans insulae function.