A practical fully automated radiosynthesis of [¹⁸F]Flurpiridaz on the module modular lab-pharmtracer without external...

[¹⁸F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [¹⁸F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relatively long half-life, F-18 is a high-potential radionuclide for the early detection of CAD. In this study, we aimed to develop a fully automated synthesis of [¹⁸F]Flurpiridaz without further preparative HPLC purification.

Precursor 6 was obtained by multi-step synthesis starting from mucochloric acid (1) as a sole product with 35% yield and identified by spectroscopic measurement. Manually cold labeling experiments were performed using the stable isotope [¹⁹F]F, and TBA-HCO₃ PTC provided desirable fluorinated compound with high yield. A fully automated [¹⁸F]Flurpiridaz synthesis on the ML-PT device provided 55-65% radiochemical yield with more than 98% radiochemical purity. The final product purification method demonstrated that [¹⁸F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality.

A novel and fascinating strategy was developed for the fully automated synthesis of [¹⁸F]Flurpiridaz (7) on ML PT. Organic synthesis of precursor 6 was achieved with a desirable yield and characterized by NMR and HR-MS. A detailed set of cold experiments were completed for optimization conditions before hot trials and TBA-HCO₃ increased molar activity with a minimum amount of side products. Radiolabeling showed that our self-designed automated synthesis method enables high radiochemical yield and radiochemical purity for the production of [¹⁸F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [¹⁸F]Flurpiridaz (7) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations.