18F-硝基咪唑的放化稳定性

    Radiochemical Stability of 18F-FMISO

    • 摘要: 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。

       

      Abstract: 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.

       

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