PT - JOURNAL ARTICLE AU - Lukas Kessler AU - Justin Ferdinandus AU - Nader Hirmas AU - Sebastian Bauer AU - Uta Dirksen AU - Fadi Zarrad AU - Michael Nader AU - Michal Chodyla AU - Aleksandar Milosevic AU - Lale Umutlu AU - Martin Schuler AU - Lars Erik Podleska AU - Hans-Ulrich Schildhaus AU - Wolfgang P. Fendler AU - Rainer Hamacher TI - <sup>68</sup>Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the <sup>68</sup>Ga-FAPI PET Prospective Observational Trial AID - 10.2967/jnumed.121.262096 DP - 2022 Jan 01 TA - Journal of Nuclear Medicine PG - 89--95 VI - 63 IP - 1 4099 - http://jnm.snmjournals.org/content/63/1/89.short 4100 - http://jnm.snmjournals.org/content/63/1/89.full SO - J Nucl Med2022 Jan 01; 63 AB - Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87–1.00) on a per-patient and 0.97 (95% CI, 0.84–1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82–1.00) on a per-patient and 0.94 (95% CI, 0.80–0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.