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In Vivo/In Vitro Characterisation of a Novel MAO-B Inhibitor Radioligand, Fluorine-18 Labeled Deuterated Fluorodeprenyl (18F-Fluorodeprenyl-D2).

Nag, Sangram; Fazio, Patrik; Lehmann, Lutz; Kettschau, Georg; Heinrich, Tobias; Thiele, Andrea; Svedberg, Marie; Amini, Nahid; Leesch, Samira; Catafau, Ana; Hannestad, Jonas; Varrone, Andrea; Halldin, Christer


The aim of this study was to radiolabel a novel bis-deuterium substituted L-deprenyl analogue (18F-fluorodeprenyl-D2) with fluorine-18 and to evaluate its potential to visualize and quantify monoamine oxidase B (MAO-B) activity in vivo.


The precursor compound (5a + 5b) and reference standard (6) were synthesized in multi-step syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used in order to determine IC50 values. Radiolabeling was accomplished by nucleophilic substitution reaction. Whole hemisphere autoradiography (ARG) was performed with 18F-fluorodeprenyl-D2. A positron emission tomography (PET) study was carried out in a cynomolgus monkey. Radiometabolites were measured in monkey plasma using HPLC.


Compound 6 inhibited MAO-B with an IC50 of 227 ± 36.8 nM and for MAO-A >2000 nM. Radiolabeling was accomplished with high radiochemical yield, purity and specific radioactivity. The ARG 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 wash-out from the brain. Regional time activity curves were better described by 2 Tissue Compartment Model. The administration 1 mg/Kg of L-Deprenyl yielded to 70 % inhibition of MAO-B in all regions. Radiometabolite studies demonstrated 20% unchanged radioligand at 120 min post injection. 18F-Fluorodeprenyl-D2 showed a less irreversible behavior than previously reported MAO-B radioligands. The results suggest that 18F-fluorodeprenyl-D2 is suitable PET radioligand for visualization of MAO-B activity in human brain.

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