叶酸可接受型显影剂（99m）Tc-DTPA-叶酸-聚合物的合成与生物学评估

Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

作者信息

Chen Fei, Shao Kejing, Zhu Bao, Jiang Mengjun

机构信息

Department of Nuclear Medicine, Nanjing Medical University, Affiliated Wuxi People's Hospital, Wuxi, Jiangsu 214023, PR China.

出版信息

Bioorg Med Chem Lett. 2016 May 15;26(10):2547-2550. doi: 10.1016/j.bmcl.2016.03.084. Epub 2016 Mar 25.

DOI:10.1016/j.bmcl.2016.03.084

PMID:27072904

Abstract

A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides.

摘要

通过传统化学合成方法制备了一种含有二乙三胺五乙酸（DTPA）片段的新型可靶向癌症的叶酸-聚甲基丙烯酸2-羟乙酯（PFDH）共聚物，随后用（99m）Tc进行标记。（99m）Tc标记的PFDH能够轻松制备，放射化学产率高达91%，放射化学纯度为95%。（99m）Tc标记的PFDH的正辛醇-水分配系数LogP值为-2.19，该放射性示踪剂在磷酸盐缓冲盐水和人血清中2小时内保持稳定（在PBS中>95%，在人血清中约90%）。为了研究（99m）Tc标记的PFDH的肿瘤靶向性、体外和体内稳定性、细胞摄取、体内生物分布以及单光子发射计算机断层显像（SPECT）成像，分别进行了评估。这些初步结果强烈表明，这种新型叶酸共轭树枝状大分子可能被开发成为递送治疗性放射性核素的潜在载体。