Hamacher_2024_J.Nucl.Med_65_252

Fibroblast activation protein alpha (FAPalpha) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPalpha in solitary fibrous tumor (SFT) and its potential use as a radiotheranostic target. Methods: We analyzed FAPalpha messenger RNA and protein expression in biopsy samples from SFT patients using immunohistochemistry and multiplexed immunofluorescence. Tracer uptake and detection efficacy were assessed in patients undergoing clinical (68)Ga-FAPalpha inhibitor (FAPI)-46 PET,(18)F-FDG PET, and contrast-enhanced CT. (90)Y-FAPI-46 radioligand therapy was offered to eligible patients with progressive SFT. Results: Among 813 patients and 126 tumor entities analyzed from the prospective observational MASTER program of the German Cancer Consortium, SFT (n = 34) had the highest median FAPalpha messenger RNA expression. Protein expression was confirmed in tumor biopsies from 29 of 38 SFT patients (76%) in an independent cohort. Most cases showed intermediate to high FAPalpha expression by immunohistochemistry (24/38 samples, 63%), which was located primarily on the tumor cell surface. Nineteen patients who underwent (68)Ga-FAPI-46 PET imaging demonstrated significantly increased tumor uptake, with an SUV(max) of 13.2 (interquartile range [IQR], 10.2), and an improved mean detection efficacy of 94.5% (SEM, 4.2%), as compared with (18)F-FDG PET (SUV(max), 3.2 [IQR, 3.1]; detection efficacy, 77.3% [SEM, 5.5%]). Eleven patients received a total of 34 cycles (median, 3 cycles [IQR, 2 cycles]) of (90)Y-FAPI-46 radioligand therapy, which resulted in disease control in 9 patients (82%). Median progression-free survival was 227 d (IQR, 220 d). Conclusion: FAPalpha is highly expressed by SFT and may serve as a target for imaging and therapy. Further studies are warranted to define the role of FAPalpha-directed theranostics in the care of SFT patients.