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目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。
OBJECTIVE: To prepare imaging agents targeting glioma by radioactive nuclide ~ (99m) Tc labeling of BmK CT polypeptide and to investigate the feasibility of 99m Tc-BmK CT in the imaging of glioma. Methods: BmK CT-DTPA was obtained by reaction of the free amino group of BmK CT with DTPA anhydride. 99m Tc-BmK CT was isolated and purified by column chromatography after 99m Tc labeling. The radiochemical purity of the marker at different time points in PBS solution and serum was determined to evaluate the stability of BmK CT- 99m Tc in vitro. New Zealand White rabbits intravenous injection of ~ (99m) Tc-BmK CT SPECT imaging, observed at different time points in vivo radioactive distribution. (99m) Tc-BmK CT was injected into the tail vein of nude mice to observe the tumor uptake at different time points. The nude mice were sacrificed 4 h after injection, and the tumors and major organs were isolated for SPECT imaging. ROI analysis of relative radioactivity count. Results: The labeling rate of ~ (99m) Tc labeled BmK CT polypeptide was more than 80%. After purification by column chromatography, the radioactive chemical purity was more than 99%. The stability of the marker in PBS and serum was good. The radioactive chemical purity was higher than 95% within 6 h and the radiochemical purity was above 90% within 12 h. SPECT imaging of normal white rabbits showed that ~ (99m) Tc-BmK CT was mainly concentrated in the liver, spleen and kidney, the soft tissue continued to develop weakly, no nuclide was found in the thyroid gland and gastrointestinal tract, and the imaging agent was mainly excreted through the urinary system , 24 h kidney and liver development close. SPECT imaging of glioma in nude mice showed that the tumor was clearly visualized 4 h after injection, and the ROI analysis showed a tumor / muscle ratio of 4.26 ± 0.25. The metabolites of the markers were slowly metabolized in the tumor and remained relatively high at 8 h. CONCLUSION: The ~ (99m) Tc-labeled BmK CT polypeptide was successfully prepared in this study. The marker was mainly up-regulated by the liver, spleen and kidney and excreted through the urinary system. 99m Tc-BmK CT could accumulate in subcutaneous glioma , 4 h after injection of tumor development clear, slow metabolism within the tumor, has the potential to become a new glioma molecular probe.