PT - JOURNAL ARTICLE AU - Zhao, Liang AU - Wen, Xuejun AU - Xu, Weizhi AU - Pang, Yizhen AU - Sun, Long AU - Wu, Xiaoming AU - Xu, Pengfei AU - Zhang, Jingjing AU - Guo, Zhide AU - Lin, Qin AU - Chen, Xiaoyuan AU - Chen, Haojun TI - 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 AID - 10.2967/jnumed.122.265383 DP - 2023 Aug 01 TA - Journal of Nuclear Medicine PG - 1210--1217 VI - 64 IP - 8 4099 - http://jnm.snmjournals.org/content/64/8/1210.short 4100 - http://jnm.snmjournals.org/content/64/8/1210.full SO - J Nucl Med2023 Aug 01; 64 AB - Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin αvβ3–positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with 68Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FAP and integrin αvβ3, would be advantageous because of its dual-receptor–targeting property. Methods: The effective dose of 68Ga-FAPI-RGD was evaluated in 3 healthy volunteers. The clinical feasibility of 68Ga-FAPI-RGD PET/CT was evaluated in 22 patients with various types of cancer, and the results were compared with those of 18F-FDG and 68Ga-FAPI-46. Results: 68Ga-FAPI-RGD was tolerated well, with no adverse events in any of the healthy volunteers or patients. The effective dose from 68Ga-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 68Ga-FAPI-RGD PET/CT were significantly higher than those in 18F-FDG PET/CT (primary tumors: SUVmax, 18.0 vs. 9.1 [P &lt; 0.001], and TBR, 15.2 vs. 5.5 [P &lt; 0.001]; lymph node metastases: SUVmax, 12.1 vs. 6.1 [P &lt; 0.001], and TBR, 13.3 vs. 4.1 [P &lt; 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. 68Ga-FAPI-RGD PET/CT also yielded a higher radiotracer uptake and TBR than 68Ga-FAPI-46 PET/CT did. Conclusion: 68Ga-FAPI-RGD exhibited improved tumor uptake and TBR compared with 18F-FDG and 68Ga-FAPI PET/CT. This study demonstrated the safety and clinical feasibility of 68Ga-FAPI-RGD PET/CT for imaging of various types of cancer.