Lanzafame_2024_J.Nucl.Med_65_880

Fibroblast activation protein-alpha (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of (68)Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of (68)Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent (68)Ga-FAPI PET/CT and (18)F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUV(max)) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of (68)Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of (68)Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUV(max) greater than 10 for all tumor regions. Results: (68)Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUV(max) +/- SD) were solitary fibrous tumor (24.7 +/- 11.9), undifferentiated pleomorphic sarcoma (18.8 +/- 13.1), and leiomyosarcoma (15.2 +/- 10.2). Uptake of (68)Ga-FAPI versus (18)F-FDG was significantly higher in low-grade sarcomas (10.4 +/- 8.5 vs. 7.0 +/- 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 +/- 12.5 vs. 8.5 +/- 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of (68)Ga-FAPI was higher than that of (18)F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). (68)Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, (68)Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of (18)F-FDG PET. (68)Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.