¹Department of Radioisotopes and Radiopharmaceuticals Production, University Institute of Positron Emission Tomography, Skopje, Macedonia
²Faculty of Medical Sciences, Goce Delcev University - Stip, Macedonia
³Institute of Pathophysiology and Nuclear Medicine, Skopje, Macedonia
⁴Medical Faculty, University “Ss Cyril and Methodius” Skopje, Macedonia DOI : 10.29228/jrp.484 The increasing number of fluorinated pharmaceuticals in pharmaceutical chemistry and fluorine radiopharmaceuticals in radiochemistry highlights the importance of optimizing their synthesis processes. [18F]Fluoromisonidazole ([18F]FMISO) radiopharmaceutical synthesized using aqueous [18F]F- and 1-(2'-nitro-1'- imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonylpropanediol precursor (NITTP), is one such example. This radiolabeled compound is used for imaging tumor hypoxia by positron emission tomography (PET). When working with ionizing radiation, ensuring the operator's safety is crucial. As a result, the synthesis process for [18F]FMISO takes place within automated modules in closed lead-shielded hot cells. This protective measure prohibits the collection of control samples during the synthesis process. Our experiments involved utilizing the stable isotope [19F]F- instead of [18F]F- to examine various aspects. These included analyzing the intermediate compound produced after the fluorination reaction, assessing unhydrolyzed/hydrolyzed intermediates, and detecting unexpected or unknown chemical impurities in both the unpurified and final purified products. HPLC analysis was employed to analyze the collected samples. The results obtained from these experiments proved invaluable in addressing the challenge of unwanted chemical impurities during the radiosynthesis of [18F]FMISO. They provided valuable insights that aided in the further development of the synthesis process. Overall, this study demonstrates the significance of utilizing nonradioactive chemistry to optimize radiosynthesis, allowing for the safe and efficient production of [18F]FMISO without the need for radiation exposure. Keywords : [¹⁸F]Fluoromisonidazole; [¹⁹F]F-; synthesis; fluorinated intermediate; impurity