摘要:
目的 改进美国CTI公乙酸盐(11CAC)自动合成模块流程,提高产量稳定性;用小鼠体内分布、小鼠和正常人体显像验证改进后产品的性能。方法 l.11CAC的制备:猝灭反应水量由原来的0.1~0.2 ml固定在0.2 ml;除杂质和蒸馈温度由135℃提高至145℃;薄层层析法检测放射化学纯度。2.改进后产品件能的验证:(1)体内分布:20只雌性小鼠随机分4组,静脉注射11C-AC后0.5 min、5 min、10 min和20 min处死,计算血及脏器的每克组织的百分注射剂量(lD%/g)。(2)显像:①小鼠2只,注射11C-AC后0.5 min及20 min显像;②正常女性志愿者3例,注射11C-AC后2例行上腹局部早期即刻及全身延迟显像,1例行全身延迟显像和脑显像。结果 1.改进前共合成11CAC 113次,其中61次产量<370 MBq;改进后17次,产量全部>370 MBq。薄层层析法Rf=0.7~0.8,放射化学纯度>90%。2.改进后产品:(1)小鼠体内分布:心、肾内放射性随时间变化最大,胰腺、骨、肝和脾有中度摄取,膀胱、脑放射性最低。(2)显像:①小鼠0.5 min时心脏显影,20 min时肝、脾显影清晰。②正常人早期心、肾及胰腺显影最清晰;延迟期心脏清除最快,肾实质内仍有少量放射性,胰腺内持续高摄取。肝、脾为中度摄取及清除,膀胱和脑内无放射性。结论 美国CT1公司提供的11C-AC自动合成模块经改进反应条件后,产量及放射化学纯度可以满足临床要求。
Abstract:
Objective To improve the stability of 11C-AC yields with CTI Inc, USA automatic synthesis module and to evaluate the product with biodistribution and imaging studies. Methods 1. Synthesis of 11C-AC. The amount of quenching water was fixed to 0.2 ml instead of fluctuating from 0.1 to 0.2 ml. The purifying and distilling temperature were raised to 140℃-145℃ instead of 135℃. Thin layer chromatography was performed on products for quality control. 2. Biodistribution studies. (1) Twenty female mice were divided into 4 groups. Each mouse was killed separately 0.5 min, 5 min, 10 min and 20 min after injection. Blood and organs were weighed and their radioactivity measured (calculated to ID%/g). (2) Two female mice were killed 0.5 min and 20 min separately after injection with 11C-AC and imaged, (3) Three female volunteers underwent PET studies after injection. Initial upper abdomen scan for 2 cases, delayed whole body scan for 3 cases and brain scan for 1 case were performed. Results (1) Synthesis of 11C-AC, A total of 113 syntheses were performed with original method. The yields of 61 syntheses were <370MBq (less than one clinical dose). After improvement, the yields of 17 syntheses were all >370 MBq (12 of them>740 MBq). The Rf of thin layer chromatograph was 0.7-0.8 and radiochemical purity>90%. (2) Biodistribution studies. The high uptake by heart and kidneys changed rapidly with time. Pancreas, liver and spleen had moderate uptake and clearance. (3) Imaging studies. In normal persons, heart, kidneys and pancreas showed high uptake in initial image and cleared rapidly from heart and kidneys, but the pancreas showed persistent high uptake in delayed image also. There was no radioactivity in bladder and brain. Conclusion The yield of 11C-AC syntheses by our improved method is stable and fulfills the requirement for clinical uses.
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