{"title":"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.","authors":"Liang Zhao, Xuejun Wen, Weizhi Xu, Yizhen Pang, Long Sun, Xiaoming Wu, Pengfei Xu, Jingjing Zhang, Zhide Guo, Qin Lin, Xiaoyuan Chen, Haojun Chen","doi":"10.2967/jnumed.122.265383","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":9.1000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394316/pdf/","citationCount":"8","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nuclear Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2967/jnumed.122.265383","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 8
Abstract
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 < 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. 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.
期刊介绍:
The Journal of Nuclear Medicine (JNM), self-published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), provides readers worldwide with clinical and basic science investigations, continuing education articles, reviews, employment opportunities, and updates on practice and research. In the 2022 Journal Citation Reports (released in June 2023), JNM ranked sixth in impact among 203 medical journals worldwide in the radiology, nuclear medicine, and medical imaging category.