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）是对前列腺癌中荷尔蒙治疗的重要肿瘤反应性。在这项研究中，我们开发了一种自动合成方法，用于[^<18> f] fdht，使用胶合式盒式盒子自动pet radiopharemaceutical合成器我们选择了tracerlab mxfdg（ge）。 ] MING并在无菌条件下对盒式布局进行修改。）磺酰氧] -3，3-（乙二基）和rostan-1 ...乙腈在125°C中加热10分钟。在室温下用NABH_4在eTranol中使用NABH_4降低。将抗焦钠作为自由基的烧瓶。 C.总合成时间的放射性产量100分钟，包括使用小鼠的质量控制，最终产物是高质量的，并且适用于临床研究。