One-step radiosynthesis of ¹⁸F-AlF-NOTA-RGD₂ for tumor angiogenesis PET imaging.
One-step radiosynthesis of ¹⁸F-AlF-NOTA-RGD₂ for tumor angiogenesis PET imaging.
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DOI：
10.1007/s00259-011-1847-4
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发表时间：
2011-09
影响因子：
9.1
通讯作者：
Cheng, Zhen
中科院分区：
文献类型：
--
作者：
Liu, Shuanglong;Liu, Hongguang;Jiang, Han;Xu, Yingding;Zhang, Hong;Cheng, Zhen
18F标记的精氨酸-甘氨酸-天冬氨酸（RGD）肽的临床翻译的主要障碍之一是费力的多步放射合成。为了促进基于RGD的正电子发射断层扫描（PET）探针在临床环境中的应用，我们在这项研究中调查的可行性使用之间的螯合反应Al 18 F和大环螯合剂共轭二聚体RGD肽作为一个简单的一步18 F标记策略的PET探针肿瘤血管生成成像的发展。首先将二聚环肽E[c（RGDyK）]2（RGD 2）与大环螯合剂1，4，7-三氮杂环壬烷-1，4，7-三乙酸（NOTA）缀合，然后将所得生物缀合物NOTA-RGD 2经由Al 18 F中间体放射性氟化以合成18 F-AlF-NOTA-RGD 2。整合素结合亲和力的肽进行了评估，通过U87 MG细胞为基础的受体结合试验，使用125 I-echistatin作为放射性配体。在皮下U87 MG胶质母细胞瘤异种移植模型中通过微PET和生物分布进一步评估18F-AlF-NOTA-RGD 2的肿瘤靶向功效和体内概况。使用Al 18F中间体在40分钟内以良好的产率成功地对NOTA-RGD 2进行18F-氟化。19 F-AlF-NOTA-RGD 2的IC 50测定为46±4.4 nM。定量microPET研究表明，18F-AlF-NOTA-RGD 2显示出高肿瘤摄取，从体内快速清除，以及良好的肿瘤与正常器官比率。NOTA-RGD 2生物偶联物已成功制备，并在一个单一的放射合成步骤中用Al 18F标记。有利的体内性能和18F-AlF-NOTA-RGD 2的短放射合成路线保证了探针和放射性标记策略的进一步优化，以加速18F标记的RGD肽的临床翻译。
One of the major obstacles of the clinical translation of 18F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al18F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step 18F labeling strategy for development of a PET probe for tumor angiogenesis imaging. Dimeric cyclic peptide E[c(RGDyK)]2 (RGD2) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD2 was then radiofluorinated via Al18F intermediate to synthesize 18F-AlF-NOTA-RGD2. Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using 125I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of 18F-AlF-NOTA-RGD2 were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution. NOTA-RGD2 was successfully 18F-fluorinated with good yield within 40 min using the Al18F intermediate. The IC50 of 19F-AlF-NOTA-RGD2 was determined to be 46±4.4 nM. Quantitative microPET studies demonstrated that 18F-AlF-NOTA-RGD2 showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios. NOTA-RGD2 bioconjugate has been successfully prepared and labeled with Al18F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of 18F-AlF-NOTA-RGD2 warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of 18F-labeled RGD peptides.
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影响因子：
9.3
作者：
Kenny, Laura M.;Coombes, R. Charles;Aboagye, Eric O.
通讯作者：
Aboagye, Eric O.
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.2967/jnumed.109.066902
发表时间：
2010-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Laverman P;McBride WJ;Sharkey RM;Eek A;Joosten L;Oyen WJ;Goldenberg DM;Boerman OC
通讯作者：
Boerman OC
影响因子：
15.8
作者：
Haubner R;Weber WA;Beer AJ;Vabuliene E;Reim D;Sarbia M;Becker KF;Goebel M;Hein R;Wester HJ;Kessler H;Schwaiger M
通讯作者：
Schwaiger M
DOI：
10.1126/science.1161621
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Podsypanina K;Du YC;Jechlinger M;Beverly LJ;Hambardzumyan D;Varmus H
通讯作者：
Varmus H