68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial

• Published in: The Journal of nuclear medicine (1978) Vol. 63; no. 1; pp. 89 - 95
• Main Authors: Kessler, Lukas, Ferdinandus, Justin, Hirmas, Nader, Bauer, Sebastian, Dirksen, Uta, Zarrad, Fadi, Nader, Michael, Chodyla, Michal, Milosevic, Aleksandar, Umutlu, Lale, Schuler, Martin, Podleska, Lars Erik, Schildhaus, Hans-Ulrich, Fendler, Wolfgang P, Hamacher, Rainer
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01-01-2022
• Subjects: Bone tumors; Clinical Investigation; Fibroblast activation protein; Fibroblasts; Medical diagnosis; Observational studies; Patients; Positron emission tomography; Sarcoma; Tumor cells; Tumors
• ISSN: 0161-5505; 1535-5667; 1535-5667
• DOI: 10.2967/jnumed.121.262096

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.