摘要
研究了乏氧显像剂18 F-硝基咪唑(18 F-FMISO)的全自动化合成方法,分析了影响18 F-FMISO放化稳定性的因素。采用回旋加速器生产出来的18 F-,传输到住友CFN-MPS200合成装置中,经QMA柱捕获后淋洗到反应管,两次干燥除去水分,再与乙腈溶解的10 mg 1-(2’-硝基-1’-咪唑基)-2-氧-四氢呋喃基-3-氧-甲苯磺酰基-丙二醇(NITTP)进行亲核取代反应。反应液用盐酸水解后加缓冲溶液中和,进入制备型高效液相进行分离。流动相采用φ=15%的乙腈水溶液,流速3 mL/min,保留时间11 min。用旋转蒸发仪脱除溶剂,再用生理盐水溶解加入稳定剂得到18 F-FMISO注射液。考察了不同活度、稳定剂、旋蒸温度对产品放化稳定性的影响,结果表明,不校正合成效率(EOS)为(45±5)%(n=20),合成时间50 min,在抗坏血酸钠做为稳定剂的情况下,6 h后产品的放化纯度为95%;而抗坏血酸和乙醇不能在50℃以上作为稳定剂。18 F-FMISO可以用CFN-MPS200合成模块全自动化合成,产品收率较高,工艺稳定,18 F-FMISO在弱碱溶液中稳定性好,为肿瘤的乏氧显像提供了临床便利。
To study the fully automated synthesis method of the hypoxic imaging agent 18 F-nitroimidazole(18 F-FMISO)and analyze the factors affecting the radiochemical stability of 18 F-FMISO,18 F-produced by the cyclotron was transferred to the Sumitomo CFN-MPS200 synthesizer,captured by the QMA column and rinsed into the reactor,dried twice to remove water,and then dissolved with acetonitrile 10 mg 1-(2’-nitrate-1’-imidazolyl)-2-oxo-tetrahydrofuran-3-oxo-tosyl-propanediol(NITTP)undergoed a nucleophilic substitution reaction.The reaction solution was hydrolyzed with hydrochloric acid and then neutralized with buffer solution,and then entered a preparative high-performance liquid phase for separation.The mobile phase was 15%acetonitrile in water,the flow rate was 3 mL/min,and the retention time was 11 min.The solvent was removed with a rotary evaporator,and then dissolved with physiological saline to add a stabilizer to obtain 18 F-FMISO injection.The effect of different specific activities,stabilizers,and rotary evaporation temperature on the radiochemical stability of the product was studied.The result shows that the EOS is(45±5)%(n=20).The synthesis time is 50 min,and the sodium ascorbate is used as a stabilizer.The radiochemical purity of the product is 95%after 6 h,and ascorbic acid and ethanol can not be used at temperatures above 50℃ as a stabilizer.18 F-FMISO can be fully automated with the CFN-MPS200 synthesizer.The product yield is high and the process is stable.18 F-FMISO is stable in weak alkaline solutions,which provides clinical convenience for hypoxic imaging of tumors.
作者
时光
钟新文
程亮
陈尚东
SHI Guang;ZHONG Xin-wen;CHENG Liang;CHEN Shang-dong(Department of Criminal Science and Technology,Jilin Police College,Changchun 130123,China;Applied Chemistry Department,Shenyang University of Chemical Technology,Shenyang 110142,China)
出处
《核化学与放射化学》
CAS
CSCD
北大核心
2020年第5期415-422,I0006,共9页
Journal of Nuclear and Radiochemistry
