Comparison of the binding of the irreversible monoamine oxidase tracers, [(11)C]clorgyline and [(11)C]l-deprenyl in brain and peripheral organs in humans.
The monoamine oxidase A and B (MAO A and B) radiotracers [(11)C]clorgyline (CLG) and [(11)C]L-deprenyl (DEP) and their deuterium labeled counterparts (CLG-D and DEP-D) were compared to determine whether their distribution and kinetics in humans are consistent with their physical, chemical and pharmacological properties and the reported ratios of MAO A:MAO B in post-mortem human tissues. Irreversible binding was consistently higher for DEP in brain, heart, kidneys and spleen but not lung where CLG >DEP and not in thyroid where there is no DEP binding. The generally higher DEP binding is consistent with its higher enzyme affinity and larger free fraction in plasma while differences in regional distribution for CLG and DEP in brain, heart, thyroid and lungs are consistent with different relative ratios of MAO A and B in humans.
Fowler
Joanna S
JS
Brookhaven National Laboratory, Chemistry Department, Bldg 555, Upton, NY 11973, USA. fowler@bnl.gov
Logan
Jean
J
Wang
Gene-Jack
GJ
Volkow
Nora D
ND
Telang
Frank
F
Ding
Yu-Shin
YS
Shea
Colleen
C
Garza
Victor
V
Xu
Youwen
Y
Li
Zizhong
Z
Alexoff
David
D
Vaska
Paul
P
Ferrieri
Richard
R
Schlyer
David
D
Zhu
Wei
W
John Gatley
S
S
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003010:Clorgyline / Q000493:pharmacokinetics*; D003903:Deuterium / Q000493:pharmacokinetics; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics; D009928:Organ Specificity; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012642:Selegiline / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D019275:Radiopharmaceuticals; D012642:Selegiline; D003903:Deuterium; D008995:Monoamine Oxidase; D003010:Clorgyline