title: Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies.
abstract: Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [(11)C]harmine, [(11)C]clorgyline, and [(11)C]befloxatone; MAO-B: [(11)C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [(11)C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [(11)C]harmine (distribution volume, r=0.86), [(11)C]clorgyline (λk3, r=0.82), and [(11)C]deprenyl-D2 (λk3 or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ∼2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality.
authors: Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. junchao_tong@camh.net
authors: Junchao
authors: J
authors: Tong
authors: Jeffrey H
authors: JH
authors: Meyer
authors: Yoshiaki
authors: Y
authors: Furukawa
authors: Isabelle
authors: I
authors: Boileau
authors: Li-Jan
authors: LJ
authors: Chang
authors: Alan A
authors: AA
authors: Wilson
authors: Sylvain
authors: S
authors: Houle
authors: Stephen J
authors: SJ
authors: Kish
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015306:Biogenic Monoamines / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000254:growth & development*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000032:analysis* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D055815:Young Adult
chemical_list: D015306:Biogenic Monoamines; D020033:Protein Isoforms; D008995:Monoamine Oxidase
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