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用于SNAP标签正电子发射断层显像(PET)成像的放射性示踪剂的研发

Development of a Radiotracer for PET Imaging of the SNAP Tag.

作者信息

Li Xinling, Yang Xiaochun, Li Zhijian, Zheng Xiaobin, Peng Yong-Jian, Lin Wenjie, Zhou Ling, Cao Dehai, Situ Minyi, Tu Qingqiang, Huang Huiqiang, Fan Wei, Feng Guokai, Zhang Xiaofei

机构信息

Department of Nuclear Medicine, Sun Yat-sen University State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfengdong Road, Guangzhou, Guangdong Province 510060, China.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfengdong Road, Guangzhou, Guangdong Province 510060, China.

出版信息

ACS Omega. 2022 Feb 23;7(9):7550-7555. doi: 10.1021/acsomega.1c05856. eCollection 2022 Mar 8.

Abstract

Cell therapies have progressed to cures for hematopoietic disorders, neurodegenerative diseases, and cancer. However, only some patients can benefit from cell therapies even with prior screening. Due to the limited clinical methods to monitor the in vivo therapeutic functions of these transferred cells over time, the uncertain prognosis is hard to attenuate. Positron emission tomography (PET) cell tracking can provide comprehensive dynamic and spatial information on the proliferation status and whole-body distribution of the therapeutic cell. In this work, we designed and synthesized the first SNAP-tagged PET radiotracer. SNAP tag is an -alkylguanine-DNA alkyltransferase that can form an irreversible bond with F-BG-surface for in vivo cell tracking based on a reporter gene system. F-BG-surface was obtained by the F-Al radiolabeling method in 32 ± 7% radiochemical yield and showed a high in vitro stability in mouse serum. SNAP-tagged cells could be selectively targeted by F-BG-surface both in vitro (4.81 ± 0.08%AD/10 cell vs 2.26 ± 0.10%AD/10 cell) and in vivo (1.90 ± 0.05 vs 0.55 ± 0.02% ID/g, < 0.01).

摘要

细胞疗法已发展到可治愈造血系统疾病、神经退行性疾病和癌症。然而,即便进行了预先筛选,也只有部分患者能从细胞疗法中获益。由于监测这些移植细胞随时间变化的体内治疗功能的临床方法有限,预后的不确定性难以缓解。正电子发射断层扫描(PET)细胞追踪可提供有关治疗性细胞增殖状态和全身分布的全面动态和空间信息。在这项工作中,我们设计并合成了首个带有SNAP标签的PET放射性示踪剂。SNAP标签是一种O6-烷基鸟嘌呤-DNA烷基转移酶,它可以基于报告基因系统与F-BG-表面形成不可逆的键,用于体内细胞追踪。通过F-Al放射性标记法以32±7%的放射化学产率获得了F-BG-表面,并且在小鼠血清中显示出高体外稳定性。带有SNAP标签的细胞在体外(4.81±0.08%ID/10细胞对2.26±0.10%ID/10细胞)和体内(1.90±0.05对0.55±0.02%ID/g,P<0.01)均可被F-BG-表面选择性靶向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49f2/8908366/19add668af72/ao1c05856_0002.jpg

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