Synthesis and biological evaluation of novel 99mTc-oxo and 99mTc-tricarbonyl complexes with C3-functionalized thymidine dithiocarbamate for tumor imaging
Synthesis and biological evaluation of novel 99mTc-oxo and 99mTc-tricarbonyl complexes with C3-functionalized thymidine dithiocarbamate for tumor imaging
复制标题
用于肿瘤成像的新型 99mTc-氧代和 99mTc-三羰基与 C3-2-功能化胸苷二硫代氨基甲酸盐配合物的合成和生物学评价
DOI：
10.1002/aoc.4424
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发表时间：
2018-08-01
影响因子：
3.9
通讯作者：
Zhang，Junbo
中科院分区：
文献类型：
--
作者：
Duan，Xiaojiang;Gan，Qianqian;Zhang，Junbo
以[99 mTc（CO）3（H2O）3]+和[99 mTc（CO）3（H2O）3]+为核，成功地合成了一种新型的C3′-功能化的胸苷二硫代氨基甲酸酯衍生物（3 'DTC-TdR）。99 mTc配合物的结构通过制备和表征相应的稳定配合物来验证。两种配合物均具有亲脂性和体外稳定性。细胞内化实验表明，99 mTcO-3 'DTC-TdR的摄取与核苷转运体有关。这些配合物在荷瘤小鼠体内的生物分布表明，它们具有较高的肿瘤摄取率，良好的肿瘤/肌肉比和肿瘤/血液比。尤其是99 mTcO-3 'DTC-TdR，在注射后4 h表现出最高的肿瘤/肌肉比和肿瘤/血液比。SPECT/CT显像显示肿瘤内有明显的蓄积，99 mTcO-3 'DTC-TdR是一种有前途的肿瘤显像候选药物。
A novel C3′‐functionalized thymidine dithiocarbamate derivative (3’DTC‐TdR) was successfully synthesized and labelled using [99mTcO]3+core and [99mTc(CO)3(H2O)3]+core with high yields. The structures of the99mTc complexes were verified by preparation and characterization of the corresponding stable rhenium complexes. Both of the complexes were lipophilic and stablein vitro. Cell internalization experiments indicated that the uptakes of99mTcO‐3’DTC‐TdR were related to nucleoside transporters. Biodistribution of these complexes in mice bearing tumor showed that they had high tumor uptakes, good tumor/muscle ratios and tumor/blood ratios. Especially for99mTcO‐3’DTC‐TdR, it exhibited the highest tumor/muscle ratio and tumor/blood ratio at 4 h post‐injection. SPECT/CT imaging studies indicated clear accumulation in tumor, suggesting99mTcO‐3’DTC‐TdR would be a promising candidate for tumor imaging.