RT Journal Article SR Electronic T1 In Vivo and In Vitro Characterization of a Novel MAO-B Inhibitor Radioligand, 18F-Labeled Deuterated Fluorodeprenyl JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 315 OP 320 DO 10.2967/jnumed.115.161083 VO 57 IS 2 A1 Sangram Nag A1 Patrik Fazio A1 Lutz Lehmann A1 Georg Kettschau A1 Tobias Heinrich A1 Andrea Thiele A1 Marie Svedberg A1 Nahid Amini A1 Samira Leesch A1 Ana M. Catafau A1 Jonas Hannestad A1 Andrea Varrone A1 Christer Halldin YR 2016 UL http://jnm.snmjournals.org/content/57/2/315.abstract AB The aim of this study was to radiolabel a novel bis-deuterium substituted l-deprenyl analog (fluorodeprenyl-D2) with 18F and to evaluate its potential to visualize and quantify monoamine oxidase (MAO) B activity in vivo. Methods: The precursor compound (5a + 5b) and reference standard (6) were synthesized in multistep syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used to determine inhibitory concentrations of 50%. Radiolabeling was accomplished by a nucleophilic substitution reaction. Whole-hemisphere autoradiography was performed with 18F-fluorodeprenyl-D2. A PET study was performed on a cynomolgus monkey. Radiometabolites were measured in monkey plasma using high-performance liquid chromatography. Results: The 50% inhibitory concentration of compound 6 for MAO-B was 227 ± 36.8 nM. Radiolabeling was accomplished with high radiochemical yield, purity, and specific radioactivity. The autoradiography binding density of 18F-fluorodeprenyl-D2 was consistent with known MAO-B expression in the human brain. In vivo, 18F-fluorodeprenyl-D2 showed favorable kinetic properties, with relatively fast washout from the brain. Regional time–activity curves were better described by the 2-tissue-compartment model. Administration of a 1 mg/kg dose of l-deprenyl yielded 70% inhibition of MAO-B in all regions. Radiometabolite studies demonstrated 20% unchanged radioligand at 120 min after injection. 18F-fluorodeprenyl-D2 showed less irreversibility than did previously reported MAO-B radioligands. Conclusion: The results suggest that 18F-fluorodeprenyl-D2 is a suitable PET radioligand for visualization of MAO-B activity in the human brain.