Rizvi Syed Faheem Askari, Naqvi Syed Ali Raza, Roohi Samina, Sherazi Tauqir A, Rasheed Rashid
Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan.
Pakistan Institute of Nuclear Science and Technology (PINSTECH), Nilore, Islamabad, Pakistan.
Mol Biol Rep. 2018 Dec;45(6):1759-1767. doi: 10.1007/s11033-018-4319-0. Epub 2018 Aug 24.
Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of β- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of LuCl (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of Lu-MGCL2 and Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.
用放射性核素标记的调节肽进行治疗是管理无法手术的受体阳性神经内分泌肿瘤患者的一种有前景的工具。由于调节肽在肿瘤细胞表面的高特异性积累以及镥 - 177放射性核素的β和γ能量光子的良好特性，肽受体镥 - 177放射性核素疗法目前已受到广泛关注。在本研究中，通过依次混合氯化镥（约185 MBq）、pH为5的醋酸铵缓冲液、龙胆酸、胃泌素肽类似物水溶液（1 mg/mL）并将反应混合物在98°C加热，用镥 - 177标记胃泌素肽类似物，这导致了高放射化学产率（>96%）。进行色谱分析以分析放射化学纯度。保质期和血清稳定性结果表明，标记的肽在长达4小时内足够稳定。肾小球滤过率研究结果显示通过肾脏的滤过适中。Lu - MGCL2和Lu - MGCL4的肾小球滤过率值分别为48 mL/min和45 mL/min。使用大鼠和兔模型进行的生物分布和闪烁扫描研究显示非靶标积累极少，肝脏和肾脏有适度摄取。Lu - MGCL2和4的有前景的放射化学产率、稳定性、肾小球滤过率值和生物分布结果表明，这些制剂可用于肽受体放射性核素治疗（PRRT）程序的临床测试。
