Gaonkar Raghuvir H, Ganguly Soumya, Baishya Rinku, Dewanjee Saikat, Sinha Samarendu, Gupta Amit, Ganguly Shantanu, Debnath Mita C
1 Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology , Kolkata, India .
2 Department of Pharmaceutical Technology, Jadavpur University , Kolkata, India .
Cancer Biother Radiopharm. 2016 Apr;31(3):110-7. doi: 10.1089/cbr.2015.1915.
In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with (99m)Tc(CO)3(H2O)3 metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.
近年来，作者报道了(99m)Tc(CO)3标记的肽，其可作为生物分子或放射性药物向肿瘤的载体。在该项工作的延续中，他们报道了一种五肽（Met-Phe-Phe-Gly-His；肽-1）、一种六肽（Met-Phe-Phe-Asp-Gly-His；肽-2）和一种四肽（Asp-Gly-Arg-His；肽-3）的合成，以及3-氨基-1,2,4-三唑与肽-2和肽-3中天冬氨酸单元的β羧基功能的连接。这些药效基团用(99m)Tc(CO)3(H2O)3金属水合离子进行了高产率的放射性标记，对其在血清、盐水以及组氨酸溶液中的稳定性进行了表征，发现其相当稳定。B16F10细胞系结合研究显示出良好的摄取和内化。在荷诱导肿瘤的小鼠中评估了放射性标记的三唑基肽的体内行为。(99m)Tc(CO)3-三唑基肽-3显示出快速的尿清除率和相对较好的肿瘤摄取。成像研究显示使用(99m)Tc(CO)3-三唑基肽-3可观察到肿瘤，但由于腹部背景较高，肿瘤边界显示不清。基于这些结果，将进一步开展用三唑基肽靶向肿瘤的实验。
