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

雄激素受体（AR）表达是预测前列腺癌对激素治疗反应性的重要因素。16β-[^<18>F]氟-5 α-二氢睾酮（[^<18>F] FDHT）是AR显像PET的候选放射性药物，但由于反应条件复杂，报道的方法难以采用自动化模块。在这项研究中，我们开发了一种自动合成方法[^<18>F] FDHT使用塑料盒式自动PET放射性药物合成仪。我们选择TRACERlab MXFDG（GE）作为[^<18>F] FDHT合成的模块，因为它具有灵活性编程，并可在无菌条件下接受对试剂卡布局的修改。通过改变前体用量、NaBH_4用量、标记温度、标记时间、还原和水解等因素，确定了最佳标记条件。优化条件为：16 π-[[（三氟甲基）磺酰基]氧基]-3，3-（亚乙二氧基）和1，2或4 mg 关于我们 7-一个在ABS。将乙腈与干燥的[13 F]氟化物在125℃下加热10 min<18>。蒸发所得溶液，然后在室温下用NaBH_4的乙醇溶液还原。水解，0。然后使用Cosmosil 5C_<18>-AR-2，20 mmI进行制备型HPLC。D. x 250 mm，Nacalai Tesque，50%乙腈/水，8. 0ml/min，210nm）。将所需的放射性级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，将残余物溶于10 ml盐水中，然后通过无菌0. 22μm过滤器至无热原小瓶中。NaBH_4还原反应在5 min内完成，室温下15 min水解不充分，85℃水解完全。最终产物的放化产率为13。4±4。4%（n 7）。包括制备HPLC和注射剂制备过程在内的总合成时间小于100 min。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高，适合临床研究。少

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