Qiu Lin, Bognar Christopher, Tangadanchu Vijai Kumar Reddy, Moerlein Stephen M, Gaehle Gregory G, Gropler Robert J, Perlmutter Joel S, Benzinger Tammie L S, Tu Zhude
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, 63110, United States.
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri, 63110, United States.
Appl Radiat Isot. 2025 Aug 25;226:112136. doi: 10.1016/j.apradiso.2025.112136.
We report a reliable fully automated procedure to produce a promising F-18 labeled sphingosine-1-phosphate receptor 1 (S1PR1) PET ligand, 3-((2-fluoro-4-(5-(4-(2-(fluoro-F)ethoxy)-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)benzyl) (methyl)amino)propan-1-ol ([F]FZTA) on the GE TRACERlab FX2N module, using a one-pot two-step procedure following current Good Manufacturing Practices (cGMP). The MOM-protected precursor 1 was fluorinated with no-carrier-added [F]KF, catalyzed by Kryptofix 222 under heat, to afford the intermediate [F]2. After deprotecting the MOM-group on [F]2 under acidic condition, the reaction was quenched into a neutralized solution, which was then loaded on semi-preparative HPLC for purification. The collected product [F]FZTA was trapped on Sep-Pak C18 cartridge and formulated in 10 % ethanol/saline solution for quality control. The radiosynthesis of [F]FZTA was accomplished in approximately 60 min with radiochemical yield of 13.9 ± 2.9 %, radiochemical purity >91 %, and molar activity >147 GBq/μmol (n = 3, decay corrected to end of synthesis (EOS)). We successfully achieved three consecutive validation runs and the radiopharmaceutical products met all quality control criteria and specifications of the exploratory Investigational New Drug (IND) application for use of the PET radiotracer in human subjects.
我们报告了一种可靠的全自动程序，用于在GE TRACERlab FX2N模块上按照现行药品生产质量管理规范（cGMP）采用一锅两步法制备一种有前景的F-18标记的1-磷酸鞘氨醇受体1（S1PR1）PET配体，即3-((2-氟-4-(5-(4-(2-(氟-F)乙氧基)-3-(三氟甲基)苯基)-1,2,4-恶二唑-3-基)苄基)(甲基)氨基)丙-1-醇（[F]FZTA）。用无载体添加的[F]KF对MOM保护的前体1进行氟化，在Kryptofix 222催化下加热，得到中间体[F]2。在酸性条件下对[F]2上的MOM基团进行脱保护后，将反应淬灭到中和溶液中，然后加载到半制备HPLC上进行纯化。收集的产物[F]FZTA捕获在Sep-Pak C18柱上，并配制成10%乙醇/盐溶液进行质量控制。[F]FZTA的放射合成在约60分钟内完成，放射化学产率为13.9±2.9%，放射化学纯度>91%，摩尔活度>147 GBq/μmol（n = 3，衰变校正到合成结束（EOS））。我们成功完成了连续三次验证运行，放射性药物产品符合所有质量控制标准以及该PET放射性示踪剂用于人体受试者的探索性研究性新药（IND）申请的规范。
