Automated production of radiotracer [18F]FZTA for imaging sphingosine-1-phosphate receptor 1 (S1PR1) in human

Abstract

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-¹⁸F)ethoxy)-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)benzyl) (methyl)amino)propan-1-ol ([¹⁸F]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 [¹⁸F]KF, catalyzed by Kryptofix 222 under heat, to afford the intermediate [¹⁸F]2. After deprotecting the MOM-group on [¹⁸F]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 [¹⁸F]FZTA was trapped on Sep-Pak C18 cartridge and formulated in 10 % ethanol/saline solution for quality control. The radiosynthesis of [¹⁸F]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.

Keywords: Automated radiosynthesis; Fluorine-18; Positron emission tomography; Sphingosine-1-phosphate receptor 1; [(18)F]FZTA; cGMP.