A two-step strategy to radiolabel choline phospholipids with 99mTc in S180 cell membranes via strain-promoted cyclooctyne-azide cycloaddition reaction
A two-step strategy to radiolabel choline phospholipids with 99mTc in S180 cell membranes via strain-promoted cyclooctyne-azide cycloaddition reaction
复制标题
通过菌株促进的环辛炔-叠氮环加成反应在 S180 细胞膜中用 Tc-99m 放射性标记胆碱磷脂的两步策略
DOI：
10.1016/j.bmcl.2016.10.026
复制
发表时间：
2016-11-15
影响因子：
2.7
通讯作者：
Chu, Taiwei
中科院分区：
文献类型：
--
作者：
Chen, Qingxin;Chu, Taiwei
作为肿瘤标记物，用Tc-99 m放射性标记细胞膜中的含胆碱（Cho）磷脂是一个挑战。传统的联合收割机通过大配体将金属放射性核素与Cho结合的策略破坏了Cho的生物活性，导致肿瘤/非肿瘤比率低。基于应变促进的环辛炔叠氮环加成（SPAAC）反应的预靶向策略被应用于解决这一普遍问题。合成了功能性点击子作为预靶向组分：叠氮乙基胆碱（AECho）作为肿瘤标记物，氮杂二苯并环辛炔（ADIBO）与双（2-羟苯基）胺（BPA）配体（ADIBO-BPA）缀合作为Tc-99 m（CO）（3）标记和叠氮基结合基团。体外细胞实验和体内生物分布实验均表明，通过这种两步预靶向策略，可以在细胞膜上放射性标记Cho。我们相信，这种预靶向策略确实可以提高目标特异性，并减少背景信号，以优化成像质量。(C)2016爱思唯尔有限公司版权所有
As tumor markers, the radiolabeling of choline (Cho)-containing phospholipids in cellular membranes with Tc-99m is a challenge. The conventional strategy to combine the metallic radionuclide with Cho by large ligand damages the bioactivity of Cho, resulting in low tumor-to-nontumor ratios. Pretargeting strategy based on strain-promoted cyclooctyne-azide cycloaddition (SPAAC) reaction was applied to solve this general problem. Functional click synthons were synthesized as pretargeting components: azidoethyl-choline (AECho) serves as tumor marker and azadibenzocyclooctyne (ADIBO) conjugated to bis(2-pieolyl) amine (BPA) ligand (ADIBO-BPA) as Tc-99m(CO)(3)-labeling and azido-binding group. Both in vitro cell experiment and in vivo biodistribution experiment indicate that it is versatile to radiolabel Cho in cellular membranes via this two-step pretargeting strategy. We believe that this pretargeting strategy can indeed enhance the target-specificity and also reduce background signals to optimize imaging quality. (C) 2016 Elsevier Ltd. All rights reserved.