用于肿瘤显像的^(99m)Tc标记葡萄糖衍生物的合成与生物评价  

Synthesis and biological evaluation of a ^(99m)Tc-labeled glucose derivative for tumor imaging

作　　者：李一林 张旭冉 张俊波[1] Yilin Li;Xuran Zhang;Junbo Zhang(Key Laboratory of Radiopharmaceuticals,Ministry of Education,College of Chemistry,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京师范大学化学学院,放射性药物教育部重点实验室,北京100875

出　　处：《中国科学：化学》2022年第6期963-971,共9页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:21771023,22076013);北京市科技重大专项(编号:Z181100002218033)资助项目。

摘　　要：研制性能良好、制备简便且价格低廉的新型肿瘤SPECT显像剂是国际放射性药物领域的重点前沿课题.^(99m)Tc是临床应用最多的SPECT核素.为了研制新型^(99m)Tc标记的肿瘤放射性药物,本研究合成了一种含异腈的葡萄糖衍生物(CN6DG),并将其用^(99m)Tc标记得到放射化学纯度大于95%的^(99m)Tc–CN6DG配合物.该配合物为水溶性物质(log D为−2.52±0.33)且具有良好的体内外稳定性.体外细胞摄取实验结果表明其进入肿瘤细胞与葡萄糖转运体相关.其在S180荷瘤小鼠中注射2 h后肿瘤摄取值为0.75±0.12%ID/g,肿瘤/肌肉和肿瘤/血液的比值分别为4.41,18.75.在A549荷瘤小鼠中注射2 h后肿瘤摄取值为2.62±0.23%ID/g,优于^(99m)Tc–CN5DG(1.48±0.23%ID/g),肿瘤/血液比值(52.4 vs.49.33)和肿瘤/肌肉比值(6.89 vs.24.67)具有和^(99m)Tc–CN5DG同样优良的结果.在S180和A549荷瘤鼠的SPECT/CT显像结果显示其在这两种肿瘤中均有明显的浓聚,有望发展成为新型肿瘤显像剂.The development of novel tumor-imaging agents for single-photon-emission-computed tomography(SPECT)with good performance,simple preparation and low price is a hot topic in the field of radiopharmaceutical research.^(99m)Tc is the most widely used SPECT nuclide in clinic.In order to develop a novel^(99m)Tc-labeled tumor radiopharmaceuticals,in this study,a glucose derivative(CN6DG)containing isonitriles was synthesized and it was radiolabeled with^(99m)Tc to obtain the^(99m)Tc-CN6DG complex with high radiochemical purity(>95%).The complex is hydrophilic(log D=−2.52±0.33)and has good stability in vitro and in vivo.In vitro cell-uptake assay showed that tumor cells uptake of the complex was related to glucose transporters.In S180 tumor-bearing mice 2 h after injection,the tumor-uptake value was 0.75±0.12%ID/g and the tumor/muscle,tumor/blood ratios were 4.41 and 18.75,respectively.In A549 tumor-bearing mice after 2 h of post-injection,the tumor-uptake value was 2.62±0.23%ID/g,which was higher than that of^(99m)Tc-CN5DG(1.48±0.23%ID/g).Its tumor/blood(52.4 vs.49.33)ratios and tumor/muscle ratios(6.89 vs.24.67)were as good as that of^(99m)Tc-CN5DG.The SPECT/CT imaging results in S180 and A549 tumor-bearing mice showed that it had significant tumor uptakes,indicating that it is a promising tumor-imaging agent.

关 键 词：肿瘤 葡萄糖 ^(99m)Tc 异腈 SPECT 

分 类 号：O641.4[理学—物理化学] R981[理学—化学]