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Development of automatic synthesis of an androgen receptor imaging tracer for positron emission tomography

正电子发射断层扫描雄激素受体成像示踪剂自动合成的研制

基本信息

批准号：
22791182
负责人：
MORI Tetsuya
金额：
$ 2.5万
依托单位：
University of Fukui
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

项目摘要

Androgen receptor(AR) expression is an important factor to predict tumor responsiveness to hormonal therapy in prostate cancer. 16β-[^<18> F] fluoro-5α-dihydrotestosterone([^<18> F] FDHT) is a candidate for AR imaging PET radiopharmaceutical, however, the reported method was difficult to adopt an automatic modules because of the complex reaction conditions. In this study, we developed an automatic synthesis method for[^<18> F] FDHT using a plastic cassette-type automatic PET radiopharmaceutical synthesizer. We chose a TRACERlab MXFDG(GE) as the module for[^<18> F] FDHT synthesis because it has the flexibility programming and accepts modification to the cassette layout in aseptic condition. Optimum labeling condition was investigated by changing several factors(amount of precursor and NaBH_4, temperature and time of labeling, reduction and hydrolysis etc.) and the optimized condition is as follows : 1, 2 or 4 mg of 16τ-[[(trifluoromethyl) sulfonyl] oxy]-3, 3-(ethylenedioxy) and rostan-1 … More 7-one in abs. acetonitrile was heated at 125℃for 10 min with dried[^<18> F] fluoride. The resultant solution was evaporated, and then reduced with NaBH_4 in ethanol at room temperature. The hydrolysis with 0. 1N HCl was carried out for 15 min. Then the preparative HPLC was performed using a Cosmosil 5C_<18>-AR-2, 20 mmI. D. x 250 mm, Nacalai Tesque, 50% acetonitrile/water, 8. 0 ml/min, 210 nm) was performed. The desired radioactive fraction was collected to a round-bottom flask containing sodium ascorbate as a radical scavenger. The solvent was removed in vacuo and the residue was dissolved in 10 ml of saline, and then passed through a sterile 0. 22μm filter to a pyrogen-free vial. The reduction using NaBH_4 was completed in 5 min. The hydrolysis was inadequacy at RT in 15 min but it was accomplished at 85℃. The radiochemical yield in the final product was 13. 4±4. 4%(n 7). The total synthesis time including the preparative HPLC and the preparation process for an injection was less than 100 min. The quality control including acute toxicity test using mouse was confirmed that the final product was high quality and adapted for clinical research. Less

雄激素受体（AR）表达是预测前列腺癌肿瘤对激素治疗反应的重要因素。 16β-[^18F]氟5α-二氢睾酮([^18F]FDHT)是AR成像PET放射性药物的候选者，然而，由于反应条件复杂，报道的方法很难采用自动模块。在本研究中，我们开发了一种使用塑料盒式自动PET放射性药物合成仪的[^<18>F]FDHT的自动合成方法。我们选择TRACERlab MXFDG(GE)作为[^<18>F] FDHT合成的模块，因为它具有灵活的编程能力并接受在无菌条件下对盒布局的修改。通过改变前驱体和NaBH_4用量、标记温度和时间、还原和水解等因素，考察了最佳标记条件，优化条件为：1、2或4 mg 16τ-[[(三氟甲基)磺酰基]氧基]-3, 3-(亚乙二氧基)和rostan-1 … More 7-one。将乙腈与干燥的[^ 18 F]氟化物一起在125℃加热10分钟。将所得溶液蒸发，然后在室温下用NaBH_4的乙醇溶液还原。用0.1N HCl水解15分钟。然后使用Cosmosil 5C_ 18 -AR-2，20mmI进行制备型HPLC。进行D.x 250mm，Nacalai Tesque，50％乙腈/水，8.0ml/min，210nm)。将所需的放射性部分收集到含有抗坏血酸钠作为自由基清除剂的圆底烧瓶中。真空除去溶剂，将残余物溶解在10ml盐水中，然后通过无菌0。22μm过滤器至无热原小瓶中。使用NaBH_4的还原在5分钟内完成。在室温下15分钟内水解不充分，但在85℃下完成。最终产物的放射化学产率为13。4±4。 4%（n 7）。包括制备型HPLC和注射剂制备过程的总合成时间不到100分钟。包括小鼠急性毒性试验在内的质量控制证实最终产品质量优良，适合临床研究。较少的