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

Abstract

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. 68 Ga-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 68 Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent 18 F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of 68 Ga-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.

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

“…FAP is expressed in both the stroma and on neoplastic cells in sarcomas and thus appears important to sarcoma development [42,109,110]. Thus, FAPI-PET/CT might represent a viable imaging and possible therapeutic tool for sarcomas [111,112]. The prospective observational trial by Kessler et al even established a correlation between a cancerous FAPI accumulation and a histopathological FAP expression as well as a rather high positive predictive value and sensitivity of FAPI-PET/CT [111].…”

“…Thus, FAPI-PET/CT might represent a viable imaging and possible therapeutic tool for sarcomas [111,112]. The prospective observational trial by Kessler et al even established a correlation between a cancerous FAPI accumulation and a histopathological FAP expression as well as a rather high positive predictive value and sensitivity of FAPI-PET/CT [111]. Additional research is required to realize the full potential of FAP expression and FAPI-PET/CT in sarcomas.…”

Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management

“…Dendl et al (55) Gynecological malignancies 31 68 Ga FAPI PET/CT seems to be a more promising imaging modality for staging and follow-up of gynecological tumors compared with 18 F-FDG PET/CT Koerber et al (56) Several types of sarcoma 15 68 Ga-FAPI PET/CT has a high potential for clinical use in patients diagnosed with sarcoma as a staging probe and tumor characterization. Kessler et al (57) Bone and soft tissue sarcomas 47 There is a correlation between tumoral FAPI uptake intensity and histopathological FAP expression in sarcoma patients, and FAPI PET has a high sensitivity. Windish et al (58) Glioblastoma 14 For target volume delineation, 68 Ga-FAPI PET outperformed MRI in detecting gross tumor volumes.…”

“…Kessler et al. ( 57 ) evaluated 47 patients with bone or soft tissue sarcomas and measured a significant association between tracer uptake and histopathological FAP expression. High sensitivity and PPV of FAPI PET resulted in upstaging in eight (13%) patients and management change in 13 (30%) patients compared with FDG-PET.…”

Theranostische Liganden: Aktuelle und zukünftige Anwendungen

“…Haberkorn et al stellen vielversprechende präklinische und klinische Daten zur Anwendung von verschiedenen FAP-Inhibitoren, insbesondere von 68 Ga-FAPI-04 zur PET-Bildgebung dar [21,24,25]. Aufgrund einer besseren Tumoraufnahme ist FAPI-46 ein vielversprechendes theranostisches Molekül für die Anwendung bei multiplen Tumorentitäten, insbesondere bei Sarkomen [26,27].…”