Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India.
Cancer Biother Radiopharm. 2009 Oct;24(5):615-20. doi: 10.1089/cbr.2008.0597.
(99m)Tc-DTPA-bis(His) conjugate has been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compound was synthesized by the covalent coupling of DTPA bis(anhydride) with L-histidine and was characterized on the basis of infrared, nuclear magnetic resonance, and mass spectroscopy. (99m)Tc-labeled compound was found stable for about 24 hour under physiologic conditions with a more than 96% radiolabeling yield. A blood kinetic study of this complex showed a biexponential pattern as well as quick washout from the blood circulation. The biologic t(1/2)(F) and t(1/2)(S) was found to be 45 +/- 0.041 minutes and 6.5 hours +/- 0.039 minutes, respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in the right thigh. The EAT tumors in the mice were readily visible in the gamma-images and showed major accumulation of the radiotracer in the kidney. Biodistribution studies revealed a high accumulation at the tumor site. Tumor-to-muscle ratios were 5.07 +/- 0.08 and 4.2 +/- 0.01 at 1 and 4 hours, respectively. The receptor binding of the (99m)Tc-DTPA-bis(His) by an established human tumor cell line (U87-MG) showed K(D) = 1.08 nM. The preliminary studies of the (99m)Tc-DTPA-bis(His) are encouraging to carrying out further in vivo experiments for targeted tumor imaging.
(99m)Tc-DTPA-bis(His) 缀合物已被合成并评估为一种潜在的肿瘤成像放射性药物。该化合物是通过 DTPA 双（酸酐）与 L-组氨酸的共价偶联合成的，并根据红外、核磁共振和质谱进行了表征。在生理条件下，标记化合物在 24 小时内稳定，放射性标记产率超过 96%。该复合物的血液动力学研究表明呈双指数模式，并且从血液循环中迅速清除。生物半衰期 (F) 和半衰期 (S) 分别为 45 +/- 0.041 分钟和 6.5 小时 +/- 0.039 分钟。在右大腿患有 Ehrlich 腹水瘤 (EAT) 肿瘤的小鼠中进行了成像和生物分布研究。小鼠中的 EAT 肿瘤在伽马图像中清晰可见，并显示放射性示踪剂在肾脏中的大量积累。生物分布研究显示在肿瘤部位有高蓄积。肿瘤与肌肉的比值分别为 5.07 +/- 0.08 和 4.2 +/- 0.01，分别在 1 小时和 4 小时。通过已建立的人类肿瘤细胞系 (U87-MG) 对 (99m)Tc-DTPA-bis(His) 的受体结合研究表明 K(D) = 1.08 nM。(99m)Tc-DTPA-bis(His) 的初步研究令人鼓舞，可为靶向肿瘤成像进行进一步的体内实验。
