⁶⁸Ga-FAPI PET/CT for Differentiation of Malignant Peripheral Nerve Sheath Tumors, Neurofibromas, and Schwannomas

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas that can develop either de novo or as a result of malignant transformation of neurofibromas. Diagnostic modalities of choice, such as MRI or ¹⁸F-FDG PET/CT, show high sensitivity for the detection of MPNSTs but moderate specificity, as MPNSTs and benign peripheral nerve sheath tumors (BPNSTs) can initially present similar clinical and radiologic pictures. PET/CT with ⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) showed specific uptake in sarcomas and enabled differentiation of benign and malignant lesions in other entities. Here, we analyzed the ability of ⁶⁸Ga-FAPI PET/CT to differentiate between MPNSTs and BPNSTs. Methods: Twenty-six patients with suspected or histologically confirmed peripheral nerve sheath tumors who were scheduled to have surgical resection/biopsy underwent ⁶⁸Ga-FAPI-46 PET/CT with static and dynamic acquisition. SUV_max, SUV_mean, maximum and mean tumor-to-background ratios, and time-activity curves were evaluated using volume-of-interest-based analysis (isocontour 50%). Time to peak was derived from time-activity curves. Statistical analyses were performed, and receiver-operating-characteristic curves were calculated. Exemplary target validation by fibroblast activation protein immunohistochemistry was performed in 13 cases. Results: Eighteen patients (4 with MPNSTs, 5 with neurofibromas, 9 with schwannomas) were included in the final analysis. MPNSTs showed significantly higher ⁶⁸Ga-FAPI uptake compared with BPNSTs. Neurofibromas showed higher ⁶⁸Ga-FAPI uptake compared with schwannomas. In dynamic imaging, time to peak of MPNSTs and neurofibromas was prolonged compared with schwannomas. Analysis of receiver-operating-characteristic curves displayed high sensitivity (100%) and specificity (92.86%) of ⁶⁸Ga-FAPI PET/CT for discrimination of MPNSTs and BPNSTs, for an exploratory SUV_max cutoff value of 7.53. Fibroblast activation protein expression was strong in MPNSTs and moderate in BPNSTs. Conclusion: ⁶⁸Ga-FAPI PET/CT may aid in differentiating between MPNSTs and BPNSTs, thereby improving lesion characterization in indeterminate MRI or ¹⁸F-FDG PET/CT scenarios.