Monoamine oxidase A imaging in peripheral organs in healthy human subjects.
Monoamine oxidase (MAO) catalyzes the oxidative deamination of many biogenic and dietary amines. Though studies of MAO have focused mainly on its regulatory role in the brain, MAO in peripheral organs also represents a vast mechanism for detoxifying vasoactive compounds as well as for terminating the action of physiologically active amines, which can cross the blood brain barrier. Indeed, robust central and peripheral MAO activity is a major requirement in the safe use of many CNS drugs, particularly antidepressants, and thus an awareness of the MAO inhibitory potential of drugs is essential in therapeutics. In this study, we examined the feasibility of quantifying MAO A in peripheral organs in healthy human subjects using comparative positron emission tomography (PET) imaging with carbon-11 (t(1/2): 20.4 min) labeled clorgyline ([(11)C]clorgyline) a suicide inactivator of MAO A and its deuterium labeled counterpart ([(11)C]clorgyline-D2). Heart, lungs, kidneys, thyroid, and spleen showed a robust deuterium isotope effect characteristic of MAO and the magnitude of the effect was similar to that of trancylcypromine, an irreversible MAO inhibitor used in the treatment of depression. Liver time-activity curves were not affected by deuterium substitution precluding the estimation of liver MAO in vivo. In organs showing an isotope effect, MAO A is greatest in the lungs and kidneys followed by the thyroid and heart. This method, which has been previously applied in the human brain, opens the possibility to also directly assess the effects of different variables including smoking, dietary substances, drugs, disease, and genetics on peripheral MAO A in humans.
Fowler
Joanna S
JS
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. fowler@bnl.gov
Logan
Jean
J
Wang
Gene-Jack
GJ
Franceschi
Dinko
D
Volkow
Nora D
ND
Telang
Frank
F
Pappas
Naomi
N
Ferrieri
Richard
R
Shea
Colleen
C
Garza
Victor
V
Xu
Youwen
Y
King
Payton
P
Schlyer
David
D
Gatley
S John
SJ
Ding
Yu-Shin
YS
Warner
Donald
D
Netusil
Noelwah
N
Carter
Pauline
P
Jayne
Millard
M
Alexoff
David
D
Zhu
Wei
W
Vaska
Paul
P
D000328:Adult; D003010:Clorgyline / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D012016:Reference Values; D013154:Spleen / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014781:Viscera / Q000378:metabolism*
D008995:Monoamine Oxidase; D003010:Clorgyline