Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [ 68 Ga]Ga-FAPI-RGD

作者：Jie Zang, Xuejun Wen, Rong Lin, Xinying Zeng, Chao Wang, Mengqi Shi, Xueyuan Zeng, Jiaying Zhang, Xiaoming Wu, Xianzhong Zhang, Weibing Miao, Peng‐Fei Xu, Zhide Guo, Jingjing Zhang, Xiaoyuan Chen · 发表于：Theranostics · 年份：2022 · DOI：10.7150/thno.79144 · 被引用次数：88 · 研究领域：Peptidase Inhibition and Analysis、Cardiac Structural Anomalies and Repair、Protease and Inhibitor Mechanisms

To enhance tumor uptake and retention, we designed and developed bi-specific heterodimeric radiotracers targeting both FAP and v3, [ 68 Ga]Ga-FAPI-RGD. The present study aimed to evaluate the specificity, pharmacokinetics, and dosimetry of [ 68 Ga]Ga-FAPI-RGD by preclinical and preliminary clinical studies. Methods: FAPI-RGD was designed and synthesized with the quinoline-based FAPI-02 and the cyclic RGDfK peptide. Preclinical pharmacokinetics were determined in Panc02 xenograft model using microPET and biodistribution experiments. The safety and effective dosimetry of [ 68 Ga]Ga-FAPI-RGD was evaluated in 6 cancer patients, and compared with 2-[ 18 F]FDG imaging. Results: The [ 68 Ga]Ga-FAPI-RGD had good stability in saline for at least 4 h, and showed favorable binding affinity and specificity in vitro and in vivo. Compared to [ 68 Ga]Ga-FAPI-02 and [ 68 Ga]Ga-RGDfK, the tumor uptake and retention of [ 68 Ga]Ga-FAPI-RGD were very much enhanced than its monomeric counterparts at all the time points examined by microPET imaging. A total of 6 patients with various malignant tumors were prospectively enrolled. The effective dose of [ 68 Ga]Ga-FAPI-RGD was 1.94E-02 mSv/MBq. The biodistribution of [ 68 Ga]Ga-FAPI-RGD from 0 to 2 h after injection demonstrated rapid and high tumor uptake, prolonged tumor retention, and high tumor-to-background ratios (TBRs) which further increased over time. No significant difference in mean SUVmax of [ 68 Ga]Ga-FAPI-RGD and 2-[ 18 F]FDG was presen...