RT Journal Article
SR Electronic
T1 <sup>68</sup>Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the <sup>68</sup>Ga-FAPI PET Prospective Observational Trial
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 89
OP 95
DO 10.2967/jnumed.121.262096
VO 63
IS 1
A1 Lukas Kessler
A1 Justin Ferdinandus
A1 Nader Hirmas
A1 Sebastian Bauer
A1 Uta Dirksen
A1 Fadi Zarrad
A1 Michael Nader
A1 Michal Chodyla
A1 Aleksandar Milosevic
A1 Lale Umutlu
A1 Martin Schuler
A1 Lars Erik Podleska
A1 Hans-Ulrich Schildhaus
A1 Wolfgang P. Fendler
A1 Rainer Hamacher
YR 2022
UL http://jnm.snmjournals.org/content/63/1/89.abstract
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.