35326
doi
10.2967/jnumed.115.161083
oai:zenodo.org:35326
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Fazio, Patrik
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
Lehmann, Lutz
Bayer HealthCare AG, Global Drug Discovery, Berlin, Germany
Kettschau, Georg
Bayer HealthCare AG, Global Drug Discovery, Berlin, Germany
Heinrich, Tobias
Bayer HealthCare AG, Global Drug Discovery, Berlin, Germany
Thiele, Andrea
Bayer HealthCare AG, Global Drug Discovery, Berlin, Germany
Svedberg, Marie
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
Amini, Nahid
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
Leesch, Samira
Piramal Imaging GmbH, Berlin, Germany
Catafau, Ana
Piramal Imaging GmbH, Berlin, Germany
Hannestad, Jonas
UCB Pharma, Braineāl'Alleud, Belgium
Varrone, Andrea
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
Halldin, Christer
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
In Vivo/In Vitro Characterisation of a Novel MAO-B Inhibitor Radioligand, Fluorine-18 Labeled Deuterated Fluorodeprenyl (18F-Fluorodeprenyl-D2).
Nag, Sangram
Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm, Sweden
info:eu-repo/semantics/restrictedAccess
18F-Fluorodeprenyl-D2
monoamine oxidase
PET
<p>INTRODUCTION:</p>
<p>The aim of this study was to radiolabel a novel bis-deuterium substituted L-deprenyl analogue (<sup>18</sup>F-fluorodeprenyl-D<sub>2</sub>) with fluorine-18 and to evaluate its potential to visualize and quantify monoamine oxidase B (MAO-B) activity in vivo.</p>
<p>METHODS:</p>
<p>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 <sup>18</sup>F-fluorodeprenyl-D<sub>2</sub>. A positron emission tomography (PET) study was carried out in a cynomolgus monkey. Radiometabolites were measured in monkey plasma using HPLC.</p>
<p>RESULTS:</p>
<p>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 <sup>18</sup>F-fluorodeprenyl-D<sub>2</sub> was consistent with known MAO-B expression in the human brain. In vivo <sup>18</sup>F-fluorodeprenyl-D<sub>2</sub> 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. <sup>18</sup>F-Fluorodeprenyl-D<sub>2</sub> showed a less irreversible behavior than previously reported MAO-B radioligands. The results suggest that <sup>18</sup>F-fluorodeprenyl-D<sub>2</sub> is suitable PET radioligand for visualization of MAO-B activity in human brain.</p>
Zenodo
2015-11-19
info:eu-repo/semantics/article
620165
user-inmind
user-eu
award_title=Imaging of Neuroinflammation in Neurodegenerative Diseases; award_number=278850; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/278850; funder_id=00k4n6c32; funder_name=European Commission;
1579527503.074282
public
Journal of Nuclear Medecine
57
2
315-20
2015-11-19