PT  - JOURNAL ARTICLE
AU  - Kessler, Lukas
AU  - Ferdinandus, Justin
AU  - Hirmas, Nader
AU  - Bauer, Sebastian
AU  - Dirksen, Uta
AU  - Zarrad, Fadi
AU  - Nader, Michael
AU  - Chodyla, Michal-Kamil
AU  - Milosevic, Aleksandar
AU  - Umutlu, Lale
AU  - Schuler, Martin
AU  - Podleska, Lars Erik
AU  - Schildhaus, Hans-Ulrich
AU  - Fendler, Wolfgang Peter
AU  - Hamacher, Rainer
TI  - Ga-68-FAPI as diagnostic tool in sarcoma: Data from the FAPI-PET prospective observational trial
AID  - 10.2967/jnumed.121.262096
DP  - 2021 Apr 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.121.262096
4099  - http://jnm.snmjournals.org/content/early/2021/04/30/jnumed.121.262096.short
4100  - http://jnm.snmjournals.org/content/early/2021/04/30/jnumed.121.262096.full
AB  - Introduction: Bone and soft tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblast. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radio-labelled FAP-Inhibitors (e.g. 68Ga-FAPI46) have shown high tumor uptake in positron emission tomography (PET) in sarcoma patients. Here we report endpoints of the 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 FAPI-PET observational trial. Of these patients, 43 patients also underwent 18F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of 68Ga-FAPI-PET uptake intensity and histopathological FAP-expression analyzed with Spearman’s r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by two blinded readers. Results: Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (Spearman’s r = 0.43; P = 0.03). By histopathological 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 FAPI- and FDG-PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients FAPI-PET resulted in an upstaging compared to FDG-PET. FAPI-PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss kappa: 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 FAPI-PET. Conclusion: We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Further, using blinded reads and independent histopathological validation we report high PPV and sensitivity of FAPI-PET for sarcoma staging.