Syntheses and evaluations of the methoxy modified 99mTc-labeled triphenyl phosphonium cations: Potential radiometallic probes for multidrug resistance detection
Syntheses and evaluations of the methoxy modified 99mTc-labeled triphenyl phosphonium cations: Potential radiometallic probes for multidrug resistance detection
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甲氧基修饰的 99m Tc 标记的三苯基鏻阳离子的合成和评估：用于多药耐药性检测的潜在放射性金属探针
DOI：
10.1016/j.jorganchem.2018.07.003
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发表时间：
2018-09-15
影响因子：
2.3
通讯作者：
Lu, Jie
中科院分区：
文献类型：
--
作者：
Li, Xiaoyan;Chen, Shuting;Lu, Jie
为了开发新型的放射性金属标记探针用于肿瘤多药耐药（MDR）检测，以二茂铁为前体，合成了两种含甲氧基的[（C5 H4-R）Tc-99 m（CO）（3）]-三苯基膦（TPP）阳离子Tc-99 m-6和Tc-99 m-7，并通过Radio-HPLC进行了纯化。还合成了相应的Re化合物，并表征为Tc-99 m标记配合物的结构参考同系物。Tc-99 m标记的复合物是亲脂性的，并且在室温下在盐水中和在37 ℃下在小鼠血清中稳定4小时。体外细胞摄取实验表明，Tc-99 m-6和Tc-99 m-7在MDR阴性的U87肿瘤细胞中的蓄积量高于在MDR阳性的MCF-7/ADR细胞中的蓄积量。维拉帕米、环孢素A和MK 571（P-糖蛋白/MRP 1的调节剂）预处理可显著增加MCF-7/ADR细胞的放射蓄积。在生物分布研究中，注射后1h，Tc-99 m-6和Tc-99 m-7的U87肿瘤（MDR-）摄取分别为2.14 ± 0.31%ID/g和1.21 ± 0.46%ID/g，其显著高于MCF-7/ADR肿瘤中的那些（注射后1小时为0.26 +/-0.16%ID/g和0.28 +/-0.06%ID/g）。结果表明，两种Tc-99 m标记的复合物均为P-gp/MRP 1的底物。对甲氧基修饰的TPP配合物Tc-99 m-6可能在肿瘤多药耐药检测中具有更高的敏感性。(C)2018 Elsevier B.V版权所有。
In order to develop novel radio-metal labeled probes for tumor multidrug resistance (MDR) detection, two [(C5H4-R)Tc-99m(CO)(3)]-triphenylphosphonium (TPP) cations with methoxy groups, Tc-99m-6 and Tc-99m-7 were prepared from the ferrocenyl precursors and purified by Radio-HPLC. Corresponding Re compounds were also synthesized and characterized as structure-referenced congeners of Tc-99m-labeled complexes. The Tc-99m-labeled complexes were lipophilic and stable both in saline at room temperature and in mouse serum at 37 degrees C for 4 h. In vitro cell uptake assay showed that Tc-99m-6 and Tc-99m-7 had a higher accumulation in the MDR-negative U87 tumor cells than that in the MDR-positive MCF-7/ADR cells. Pre-treatment of verapamil, Cyclosporine A and MK571, the modulators of P-glycoprotein/MRP1 (the principal MDR transporters in humans), could significantly increase the radio-accumulation in MCF-7/ADR cells. In biodistribution study, the U87 tumor (MDR-) uptakes of Tc-99m-6 and Tc-99m-7 were 2.14 +/- 0.31 %ID/g and 1.21 0.46 %ID/g at 1 h post-injection respectively, which were significantly higher than those in MCF-7/ADR tumor (0.26 +/- 0.16 %ID/g and 0.28 +/- 0.06 %ID/g at 1 h post-injection). The results demonstrated both of the Tc-99m-labeled complexes were the substrates of P-gp/MRP1. The para-methoxy group modified TPP-based complex Tc-99m-6 may be more sensitive in tumor multidrug resistance detection. (C) 2018 Elsevier B.V All rights reserved.