Department of Nuclear Medicine, Infectious Disease and Immunology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.
Amino Acids. 2013 Mar;44(3):933-46. doi: 10.1007/s00726-012-1423-7. Epub 2012 Oct 23.
Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, (1)H NMR, (13)C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with (99m)Tc using Tricine and EDDA as coligands by SnCl(2) method to get products with excellent radiochemical purity >99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Internalization studies were done and IC(50) values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC(50) values of (99m)Tc-HYNIC-His(3)-Octreotate (21 ± 0.93 nM) and (99m)Tc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging somatostatin receptor-positive tumors.
肽在核医学中的靶向肿瘤诊断和治疗方面越来越受到关注。因此，我们通过 Fmoc 固相肽合成法合成了新的与 HYNIC 偶联的环状八肽。这些肽通过 RP-HPLC、MALDI 质谱、(1)H NMR、(13)C NMR、HSQC、HMBC、COSY 和 IR 光谱进行了纯化和分析。肽的构象分析通过圆二色光谱法在纯水中和三氟乙醇-水（1:1）中进行，显示出存在强的二级结构特征，如β-折叠和无规卷曲。用 Tricine 和 EDDA 作为共配体，通过 SnCl(2)法用 (99m)Tc 标记，得到放射性化学纯度>99.5%的产物。代谢稳定性分析没有显示出标记化合物断裂和形成游离 (99m)Tc 的任何证据。进行了内化研究，并在表达生长抑素受体的 C6 神经胶质瘤细胞系和大鼠脑皮质膜中测定了 IC(50)值，并与 HYNIC-TOC 作为标准进行了比较。(99m)Tc-HYNIC-His(3)-Octreotate（21±0.93 nM）和 (99m)Tc-HYNIC-TOC（2.87±0.41 nM）的 IC(50)值证明是相当的。在伽马相机下对正常大鼠进行的生物分布和成像研究显示，肾脏和尿液中的摄取非常高，表明肾脏是代谢和排泄的主要器官。在荷 C6 神经胶质瘤肿瘤的大鼠中进行的生物分布和成像研究发现，肿瘤（1.27±0.15）和胰腺（1.71±0.03）的摄取量很高。利用这些发现，可以制备新的衍生物，开发用于成像生长抑素受体阳性肿瘤的 (99m)Tc 放射性药物。
