A head-to-head comparison of [68Ga]Ga-FAPI-RGD and 2-[18F]FDG/ [68Ga]Ga-FAPI-02 PET/CT in patients with various cancers

Introduction: This head-to-head study was designed to investigate the radiotracer uptake and clinical feasibility of [⁶⁸Ga]Ga-FAPI-RGD, a bispecific heterodimeric radiotracer targeting both FAP and α_vβ₃, for detecting the primary and metastatic lesions in patients with various types of cancer, and compared the results with 2-[¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-FAPI-02 PET/CT.

Methods: Fifty-six patients with 10 different kinds of cancers were enrolled in this study. Among them, 45 patients underwent paired [⁶⁸Ga]Ga-FAPI-RGD and 2-[¹⁸F]FDG PET/CT, and the other 11 patients underwent paired [⁶⁸Ga]Ga-FAPI-RGD and [⁶⁸Ga]Ga-FAPI-02 PET/CT. The final diagnosis was based on histopathological results (n = 50) and diagnostic radiology (comprehensive considerations of imaging findings, n = 6). In addition to visual analysis, standardized uptake value (SUV) and tumor-to-background (TBR) were measured for semiquantitative comparison and correlation analysis.

Results: [⁶⁸Ga]Ga-FAPI-RGD PET/CT detected all 50 primary tumors, whereas 2-[¹⁸F]FDG PET/CT was visually positive for 43 primary tumors (P = 0.016). Furthermore, subgroup analysis revealed that of [⁶⁸Ga]Ga-FAPI-RGD PET/CT was superior to 2-[¹⁸F]FDG in renal cell carcinoma and liver cancer, but inferior to 2-[¹⁸F]FDG PET/CT in lung cancer as well as head and neck cancer. In gastric cancer, esophagus cancer, breast cancer, intestinal cancer, gliomas, and pancreatic cancer, the quantitative tumor uptake of [68Ga]Ga-FAPI-RGD was noninferior to that of 2-[¹⁸F]FDG. For metastatic tumors, [⁶⁸Ga]Ga-FAPI-RGD PET/CT revealed more PET-positive lesions and higher SUVmax for skeletal metastases (n，218 vs. 154, P = 0.043; SUVmax, 6.97 ± 3.24 vs. 5.30 ± 3.73, P = 0.04) and peritoneal metastasis (35 vs. 28, P = 0.317; SUVmax, 6.88 ± 2.92 vs. 4.70 ± 1.89, P = 0.028) compared to 2-[¹⁸F]FDG. In the comparison of [⁶⁸Ga]Ga-FAPI-RGD and [⁶⁸Ga]Ga-FAPI-02 PET/CT, [⁶⁸Ga]Ga-FAPI-RGD PET/CT identified all 11 primary tumors, whereas [⁶⁸Ga]Ga-FAPI-02 PET/CT detected 8 primary tumors (P = 0.250); and the SUVmax and TBR of primary tumors on [⁶⁸Ga]Ga-FAPI-RGD PET/CT were much higher than those on [⁶⁸Ga]Ga-FAPI-02 PET/CT (SUVmax: 9.16 ± 4.97 vs. 2.36 ± 0.94, P = 0.003; TBR: 10.23 ± 6.21 vs. 3.54 ± 1.15, P = 0.003). For metastatic tumors, the SUVmax and TBR from [⁶⁸Ga]Ga-FAPI-RGD PET/CT were higher than those from [⁶⁸Ga]Ga-FAPI-02 (SUVmax: 6.30 ± 1.87 vs. 2.02 ± 0.28, P = 0.000; TBR: 5.69 ± 3.39 vs. 1.69 ± 0.67, P = 0.001).

Conclusions: [⁶⁸Ga]Ga-FAPI-RGD is a promising new diagnostic PET tracer for imaging various kinds of cancer, in particular renal cell carcinoma, liver cancer, skeletal metastases and peritoneal metastasis.