Chen Yuan, Guo Hongjuan, Xie Fang, Lu Jie
Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education; College of Chemistry, Beijing Normal University, Beijing, 100875, China.
J Labelled Comp Radiopharm. 2014 Jan;57(1):12-7. doi: 10.1002/jlcr.3116. Epub 2013 Sep 23.
In order to develop a novel (99m) Tc-labeled folate receptor (FR) imaging agent, a dithiocarbamate derivative, pteroyl-lys-DTC, was synthesized and radiolabeled with (99m) Tc through the (99m) TcN intermediate. The radiochemical purity of the corresponding (99m) Tc-complex, (99m) TcN-pteroyl-lys-DTC, was over 95% as measured by reversed-phase HPLC. The (99m) TcN complex was stable under physiological conditions. (99m) TcN-pteroyl-lys-DTC exhibited specific FR binding in FR-positive KB cells in vitro. The biodistribution in tumor-bearing mice showed that the (99m) TcN-labeled radiotracer had good uptake (3.56 ± 0.09%ID/g at 2 h postinjection) in FR-positive KB tumors, as well as in the kidneys (30.34 ± 3.53%ID/g at 2 h postinjection). After coinjection with excess folic acid, the uptake in tumor and kidneys was significantly blocked. The results indicated that (99m) TcN-pteroyl-lys-DTC was able to target the FR-positive tumor cells and tissues specifically both in vitro and in vivo.
为了开发一种新型的（99m）Tc标记的叶酸受体（FR）显像剂，合成了一种二硫代氨基甲酸盐衍生物蝶酰-赖氨酸-DTC，并通过（99m）TcN中间体用（99m）Tc进行放射性标记。通过反相高效液相色谱法测定，相应的（99m）Tc配合物（99m）TcN-蝶酰-赖氨酸-DTC的放射化学纯度超过95%。（99m）TcN配合物在生理条件下稳定。（99m）TcN-蝶酰-赖氨酸-DTC在体外FR阳性的KB细胞中表现出特异性的FR结合。荷瘤小鼠体内的生物分布表明，（99m）TcN标记的放射性示踪剂在FR阳性的KB肿瘤中摄取良好（注射后2小时为3.56±0.09%ID/g），在肾脏中摄取也良好（注射后2小时为30.34±3.53%ID/g）。与过量叶酸共同注射后，肿瘤和肾脏中的摄取明显受到阻断。结果表明，（99m）TcN-蝶酰-赖氨酸-DTC在体外和体内均能特异性地靶向FR阳性的肿瘤细胞和组织。
