Clinical Evaluation of<sup>68</sup>Ga-FAPI-RGD for Imaging of Fibroblast Activation Protein and Integrin α<sub>v</sub>β<sub>3</sub>in Various Cancer Types
Liang Zhao, Xuejun Wen, Weizhi Xu, Yizhen Pang, Long Sun, Xiaoming Wu, Peng‐Fei Xu, Jingjing Zhang, Zhide Guo, Qin Lin, Xiaoyuan Chen, Haojun Chen
Abstract
Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin α<sub>v</sub>β<sub>3</sub>–positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with <sup>68</sup>Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin α<sub>v</sub>β<sub>3</sub>, would be advantageous because of its dual-receptor–targeting property. <b>Methods:</b> The effective dose of <sup>68</sup>Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of <sup>68</sup>Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of <sup>18</sup>F-FDG and <sup>68</sup>Ga-FAPI-46. <b>Results:</b><sup>68</sup>Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from <sup>68</sup>Ga-FAPI-RGD PET/CT was 1.01 × 10<sup>−2</sup> 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 <sup>68</sup>Ga-FAPI-RGD PET/CT were significantly higher than those in <sup>18</sup>F-FDG PET/CT (primary tumors: SUV<sub>max</sub>, 18.0 vs. 9.1 [<i>P</i> < 0.001], and TBR, 15.2 vs. 5.5 [<i>P</i> < 0.001]; lymph node metastases: SUV<sub>max</sub>, 12.1 vs. 6.1 [<i>P</i> < 0.001], and TBR, 13.3 vs. 4.1 [<i>P</i> < 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. <sup>68</sup>Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than <sup>68</sup>Ga-FAPI-46 PET/CT did. <b>Conclusion:</b><sup>68</sup>Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with <sup>18</sup>F-FDG and <sup>68</sup>Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of <sup>68</sup>Ga-FAPI-RGD PET/CT for imaging of various types of cancer.