Clinical Evaluation of 68Ga-FAPI-RGD for Imaging of Fibroblast Activation Protein and Integrin αvβ3 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 alpha(v)beta(3)-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with Ga-68 and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin avb3, would be advantageous because of its dual-receptor-targeting property. Methods: The effective dose of Ga-68-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of Ga-68-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of F-18-FDG and Ga-68-FAPI-46. Results: Ga-68-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from Ga-68-FAPI-RGD PET/CT was 1.01 x 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 Ga-68-FAPI-RGD PET/CT were significantly higher than those in F-18-FDG PET/CT (primary tumors: SUVmax, 18.0 vs. 9.1 [P < 0.001], and TBR, 15.2 vs. 5.5 [P < 0.001]; lymph node metastases: SUVmax, 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. Ga-68-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than (68)GaFAPI-46 PET/CT did. Conclusion: Ga-68-FAPI-RGD exhibited improved tumor uptake and TBR compared with F-18-FDG and Ga-68-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of Ga-68-FAPI-RGD PET/CT for imaging of various types of cancer.