Non-MAO A binding of clorgyline in white matter in human brain.
Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation.
Fowler
J S
JS
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. fowler@bnl.gov
Logan
J
J
Ding
Y S
YS
Franceschi
D
D
Wang
G J
GJ
Volkow
N D
ND
Pappas
N
N
Schlyer
D
D
Gatley
S J
SJ
Alexoff
D
D
Felder
C
C
Biegon
A
A
Zhu
W
W
D000328:Adult; D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D003010:Clorgyline / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014055:Tomography, Emission-Computed
D008996:Monoamine Oxidase Inhibitors; D017448:Receptors, Dopamine D2; D008995:Monoamine Oxidase; D003010:Clorgyline