Highly Efficient Radiosynthesis and Biological Evaluation of [18F]Safinamide, a Radiolabelled Anti‐Parkinsonian Drug for Positron Emission Tomography Imaging

As an add‐on drug approved for Parkinson's disease treatment, safinamide has multiple functions, such as selective and reversible monoamine oxidase‐B inhibition, voltage‐sensitive sodium/potassium channel blockage, and glutamate release inhibition. Meanwhile, safinamide shows tremendous therapeutic potential in the context of other central nervous system diseases (e. g. ischaemic stroke, amyotrophic lateral sclerosis, depression, etc.). In this work, [18F]safinamide, which is safinamide labelled by the positron‐emitting radionuclide [18F]fluorine, was synthesized automatically based on iodonium ylide precursors with high radiochemical yield and high molar activity. Density functional theory was applied to calculate the Gibbs free energy change during iodonium ylide‐mediated fluorination and to interpret the effect of tetraethylammonium (TEA+) as the counter cation in these reactions to improve the nucleophilicity of [18F/19F]fluoride. In addition, positron emission tomography studies on Sprague Dawley rats were carried out to determine the imaging characteristics, pharmacokinetics, and metabolism of the [18F]safinamide radiotracer. The results displayed the complete biodistribution of the radiotracer, especially in rat brains, and revealed that [18F]safinamide has moderate brain uptake, rapid and reversible binding kinetics, and good stability. Automated radiosynthesis of [18F]safinamide based on iodonium ylide precursors provided high yield and high molar activity. Dynamic positron emission tomography (PET) studies showed the biodistribution of [18F]safinamide in Sprague Dawley rats and revealed its rapid kinetics and reversible binding in the rat brain.