18F-硝基咪唑的放化稳定性

研究了乏氧显像剂¹⁸F-硝基咪唑（¹⁸F-FMISO）的全自动化合成方法，分析了影响¹⁸F-FMISO放化稳定性的因素。采用回旋加速器生产出来的¹⁸F^-，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18F-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。¹⁸F-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，¹⁸F-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。

Radiochemical Stability of 18F-FMISO

To study the fully automated synthesis method of the hypoxic imaging agent ¹⁸F-nitroimidazole(¹⁸F-FMISO) and analyze the factors affecting the radiochemical stability of ¹⁸F-FMISO, ¹⁸F^- 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 ¹⁸F-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. ¹⁸F-FMISO can be fully automated with the CFN-MPS200 synthesizer. The product yield is high and the process is stable. ¹⁸F-FMISO is stable in weak alkaline solutions, which provides clinical convenience for hypoxic imaging of tumors.