Clinical Evaluation of (68)Ga-FAPI-RGD for Imaging of Fibroblast Activation Protein and Integrin α(v)β(3) in Various Cancer Types

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin α(v)β(3)–positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with (68)Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin α(v)β(3), would be advantageous because of its dual-receptor–targeting property. Methods: The effective dose of (68)Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of (68)Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of (18)F-FDG and (68)Ga-FAPI-46. Results: (68)Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from (68)Ga-FAPI-RGD PET/CT was 1.01 × 10(−2) mSv/MBq. In clinical investigations with different types of cancer, the radiotracer uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in (68)Ga-FAPI-RGD PET/CT were significantly higher than those in (18)F-FDG PET/CT (primary tumors: SUV(max), 18.0 vs. 9.1 [P < 0.001], and TBR, 15.2 vs. 5.5 [P < 0.001]; lymph node metastases: SUV(max), 12.1 vs. 6.1 [P < 0.001], and TBR, 13.3 vs. 4.1 [P < 0.001]), resulting in an improved lesion detection rate and tumor delineation, particularly for the diagnosis of lymph node (99% vs. 91%) and bone (100% vs. 80%) metastases. (68)Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than (68)Ga-FAPI-46 PET/CT did. Conclusion: (68)Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with (18)F-FDG and (68)Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of (68)Ga-FAPI-RGD PET/CT for imaging of various types of cancer.