Evaluation of 68Ga-labeled iNGR peptide with tumor-penetrating motif for microPET imaging of CD13-positive tumor xenografts
Evaluation of 68Ga-labeled iNGR peptide with tumor-penetrating motif for microPET imaging of CD13-positive tumor xenografts
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评估具有肿瘤穿透基序的 68Ga 标记 iNGR 肽用于 CD13 阳性肿瘤异种移植物的 microPET 成像。
DOI：
10.1007/s13277-016-5068-0
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Wang, Jing
中科院分区：
文献类型：
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作者：
Zhao, Mingxuan;Yang, Weidong;Wang, Jing
本研究的目的是评估Ga-68标记的iNGR（含有Asn-Gly-Arg（NGR）归巢序列和CendR（R/KXXR/K）穿透基序）作为用于CD 13阳性异种移植物的microPET成像的新分子探针的功效。将合成的iNGR和NGR肽与DOTA缀合，然后用Ga-68标记。比较Ga-68-iNGR和Ga-68-NGR在体外稳定性、分配系数、结合亲和力、细胞摄取分析、体内microPET成像和CD 13阳性HT-1080和CD 13阴性HT-29细胞系中的生物分布研究的性能。体外实验结果表明，两种探针均表现出较高的放射化学纯度和稳定性，并且在与CD 13的结合亲和力方面没有观察到两种探针之间的显著差异。体内microPET/CT成像显示，HT-1080肿瘤中Ga-68-iNGR的摄取显著高于Ga-68-NGR。此外，肿瘤Ga-68-iNGR摄取可被冷NGR完全阻断，并被中和NRP-1抗体部分阻断。我们得出结论，Ga-68-iNGR通过NRP-1具有比Ga-68-NGR更高的肿瘤摄取和更好的肿瘤保留，表明CendR基序修饰是改善NGR肽性能的有前景的方法。
The aim of the study is to evaluate the efficacy of Ga-68-labeled iNGR, containing Asn-Gly-Arg (NGR) homing sequence and CendR (R/KXXR/K) penetrating motif, as a new molecular probe for microPET imaging of CD13-positive xenografts. The synthesized iNGR and NGR peptides were conjugated with DOTA and then labeled with Ga-68. Ga-68-iNGR and Ga-68-NGR were compared in the performance of the in vitro stability, partition coefficient, binding affinity, cell uptake analysis, in vivo microPET imaging, and biodistribution studies in CD13-positive HT-1080 and CD13-negative HT-29 cell lines. The in vitro results revealed that both probes exhibited high radiochemical purity and stability, and no significant difference between two probes was observed in terms of the binding affinity to CD13. In vivo microPET/CT imaging showed that the uptake of Ga-68-iNGR in HT-1080 tumor was significantly higher than that of Ga-68-NGR. Moreover, tumor Ga-68-iNGR uptake could be completely blocked by cold NGR and partially blocked by neutralizing NRP-1 antibody. We concluded that Ga-68-iNGR has a higher tumor uptake and better tumor retention than Ga-68-NGR through NRP-1, indicating that CendR motif modification is a promising method for improving NGR peptide performance.