| Autor: |
Jie, Zang, Xuejun, Wen, Rong, Lin, Xinying, Zeng, Chao, Wang, Mengqi, Shi, Xueyuan, Zeng, Jiaying, Zhang, Xiaoming, Wu, Xianzhong, Zhang, Weibing, Miao, Pengfei, Xu, Zhide, Guo, Jingjing, Zhang, Xiaoyuan, Chen |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Theranostics. 12:7180-7190 |
| ISSN: |
1838-7640 |
| DOI: |
10.7150/thno.79144 |
| Popis: |
To enhance tumor uptake and retention, we designed and developed bi-specific heterodimeric radiotracers targeting both FAP and αvβ3, [sup68/supGa]Ga-FAPI-RGD. The present study aimed to evaluate the specificity, pharmacokinetics, and dosimetry of [sup68/supGa]Ga-FAPI-RGD by preclinical and preliminary clinical studies.bMethods:/bFAPI-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 [sup68/supGa]Ga-FAPI-RGD was evaluated in 6 cancer patients, and compared with 2-[sup18/supF]FDG imaging.bResults:/bThe [sup68/supGa]Ga-FAPI-RGD had good stability in saline for at least 4 h, and showed favorable binding affinity and specificityiin vitro/iandiin vivo/i. Compared to [sup68/supGa]Ga-FAPI-02 and [sup68/supGa]Ga-RGDfK, the tumor uptake and retention of [sup68/supGa]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 [sup68/supGa]Ga-FAPI-RGD was 1.94E-02 mSv/MBq. The biodistribution of [sup68/supGa]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 [sup68/supGa]Ga-FAPI-RGD and 2-[sup18/supF]FDG was present in primary tumors (8.9±3.2ivs./i10.3 ± 6.9; p = 0.459).bConclusion:/bThe dual targeting PET tracer [sup68/supGa]Ga-FAPI-RGD showed significantly improved tumor uptake and retention, as well as cleaner background oversup68/supGa-labeled FAPI and RGD monospecific tracers. The first-in-human biodistribution study showed high TBRs over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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