Fully Automated Production of Diverse ¹⁸F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification

Abstract

Fully automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of PET tracers made under current good manufacturing practice guidelines. There is a current trend toward supporting kitlike disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers because of pressure, temperature, and chemical compatibility considerations. This study demonstrated the versatile use of the ELIXYS fully automated radiosynthesizer to adapt and produce 8 different ¹⁸F-labeled PET tracers of varying complexity. Methods: Three-reactor syntheses of 2-deoxy-2-¹⁸F-fluoro-β-d-arabinofuranosylcytosine (d-¹⁸F-FAC), 2-deoxy-2-¹⁸F-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-¹⁸F-FMAU), and 2-deoxy-2-¹⁸F-fluoro-5-ethyl-β-d-arabinofuranosyluracil (d-¹⁸F-FEAU) along with the 1-reactor syntheses of d-¹⁸F-FEAU, ¹⁸F-FDG, 3-deoxy-3-¹⁸F-fluoro-l-thymidine (¹⁸F-FLT), ¹⁸F-fallypride, 9-(4-¹⁸F-fluoro-3-hydroxymethylbutyl)-guanine (¹⁸F-FHBG), and N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F-SFB), were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted and slightly modified from those in the literature but were not fully optimized. Furthermore, ¹⁸F-FLT, ¹⁸F-FDG, and ¹⁸F-fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor–bearing severe combined immunodeficient mice and wild-type BALB/c mice. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests. Results: All tracers were produced with radiochemical yields comparable to those in the literature. ¹⁸F-FLT, ¹⁸F-FDG, and ¹⁸F-fallypride were successfully used to image the mice, with results consistent with those reported in the literature. All tracers that were subjected to clinical quality control tests passed. Conclusion: The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple ¹⁸F-labeled PET tracers suitable for clinical applications using the same hardware setup.