Automation of simplified two-step radiolabeling via ditosylate synthon for 18F-labeled radiotracers using AllinOne module

Abstract

Direct fluorination of a tosylate or mesylate precursor has been a wide-spread and reliable way for radio-fluorination. This approach can be difficult to achieve when the precursor cannot be easily obtained or is chemically unstable. A possible alternative method is to radiolabel ethylene ditosylate or 1,3-propanediol di-p-tosylate to form a radiofluorinated synthon. Here we present the automation of a simplified and reliable approach for the two-step fluorination using [¹⁸F]FP-TMP, an analog of antibacterial agent trimethoprim. We demonstrate the feasibility of purifying the fluorinated synthon via filtration, and one final HPLC purification on a commercially available Trasis AllinOne module. The overall reaction time for the two-step reaction is around 90 min andthe decay-corrected yield for more than fifty preparations of [¹⁸F]FP-TMP is 22 ± 5 % with high radiochemical purity (≥ 90 %) and specific activities (147 ± 107 GBq/μmol). All batches passed pre-established quality control specifications, demonstrating the utility of using this method in tracer syntheses that meet good manufacturing practice (GMP) requirement. This method can be adopted to the syntheses of other radiotracers, such as [¹⁸F]FE-TMP, (+)-[¹⁸F]F-PHNO and [¹⁸F]FFMZ.

Keywords: AllinOne; Automation; PET; Radiotracer; Two-step fluorination.

Fig. 1.

Synthesis scheme of four radiotracers employing two-step reaction.

Fig. 2.

The module configuration for two-step two-vessel reactions. a. AllinOne user software interface (left); b. Set up with cassettes and reagents (right).

Fig. 3.

Chromatography of Semi-Prep HPLC for [¹⁸F]FP-TMP (Top: Radioactivity; Bottom: UV).