Fibroblast Activation Protein α–Directed Imaging and Therapy of Solitary Fibrous Tumor

Abstract

Fibroblast activation protein a (FAPa) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPa in solitary fibrous tumor (SFT) and its potential use as a radio-theranostic target. Methods: We analyzed FAPa 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 68Ga-FAPa inhibitor (FAPI)–46 PET,18F-FDG PET, and contrast-enhanced CT. 90Y-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 5 34) had the highest median FAPa 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 FAPa expression by immunohistochemistry (24/ 38 samples, 63%), which was located primarily on the tumor cell surface. Nineteen patients who underwent 68Ga-FAPI-46 PET imaging demonstrated significantly increased tumor uptake, with an SUVmax of 13.2 (interquartile range [IQR], 10.2), and an improved mean detection efficacy of 94.5% (SEM, 4.2%), as compared with 18F-FDG PET (SUVmax, 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 90Y-FAPI-46 radioligand therapy, which resulted in disease control in 9 patients (82%). Median progression-free survival was 227 d (IQR, 220 d). Conclusion: FAPa is highly expressed by SFT and may serve as a target for imaging and therapy. Further studies are warranted to define the role of FAPa-directed theranostics in the care of SFT patients.