PT  - JOURNAL ARTICLE
AU  - Sangram Nag
AU  - Patrik Fazio
AU  - Lutz Lehmann
AU  - Georg Kettschau
AU  - Tobias Heinrich
AU  - Andrea Thiele
AU  - Marie Svedberg
AU  - Nahid Amini
AU  - Samira Leesch
AU  - Ana M. Catafau
AU  - Jonas Hannestad
AU  - Andrea Varrone
AU  - Christer Halldin
TI  - In Vivo and In Vitro Characterization of a Novel MAO-B Inhibitor Radioligand, <sup>18</sup>F-Labeled Deuterated Fluorodeprenyl
AID  - 10.2967/jnumed.115.161083
DP  - 2016 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 315--320
VI  - 57
IP  - 2
4099  - http://jnm.snmjournals.org/content/57/2/315.short
4100  - http://jnm.snmjournals.org/content/57/2/315.full
SO  - J Nucl Med2016 Feb 01; 57
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.