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

• Published in: EJNMMI radiopharmacy and chemistry Vol. 7; no. 1; p. 30
• Main Authors: Eryilmaz, Kurtulus, Kilbas, Benan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 05.11.2022; Springer Nature B.V; SpringerOpen
• Subjects: 18F; [18F]Flurpiridaz; Acceptance criteria; Automated synthesis; Automation; Cardiac PET; Cardiovascular disease; Chemistry; Clinical trials; Coronary vessels; Fluorine; Fluorine isotopes; High-performance liquid chromatography; Image quality; Imaging; Liquid chromatography; Medicine; Medicine & Public Health; Molecular Medicine; Nitrogen; NMR; Nuclear Chemistry; Nuclear magnetic resonance; Nuclear Medicine; Optimization; Pharmaceuticals; Pharmacotherapy; Positron emission; Precursors; Purification; Purity; Pyridaben; Radiation; Radiochemistry; Radioisotopes; Radiolabelling; Radiology; Research Article; Stable isotopes; Tomography; [; F; Automated synthesis; Cardiac PET; F]Flurpiridaz
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-022-00182-z

Background [ 18 F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [ 18 F]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 [ 18 F]Flurpiridaz without further preparative HPLC purification. Results 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 [ 19 F]F, and TBA-HCO 3 PTC provided desirable fluorinated compound with high yield. A fully automated [ 18 F]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 [ 18 F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality. Conclusion A novel and fascinating strategy was developed for the fully automated synthesis of [ 18 F]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-HCO 3 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 [ 18 F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [ 18 F]Flurpiridaz ( 7 ) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations.