Monoamine oxidase: Radiotracer chemistry and human studies

Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

doi:10.1002/jlcr.3247

Title: Monoamine oxidase: Radiotracer chemistry and human studies

Journal Article · Sat Feb 28 23:00:00 EST 2015 · Journal of Labelled Compounds and Radiopharmaceuticals

DOI: https://doi.org/10.1002/jlcr.3247 · OSTI ID:1183290

Fowler, Joanna S. ^[1]; Logan, Jean ^[2]; Shumay, Elena ^[3]; Alia-Klein, Nelly ^[4]; Wang, Gene-Jack ^[3]; Volkow, Nora D. ^[5]

Brookhaven National Lab. (BNL), Upton, NY (United States)
New York Univ., Langone Medical Center, New York, NY (United States)
National Inst. on Alcohol Abuse and Alcoholism, National Inst. of Health, Betheseda, MD (United States)
Mount Sinai School of Medicine, New York, NY (United States)
National Inst. on Alcohol Abuse and Alcoholism, National Inst. of Health, Betheseda, MD (United States); National Inst. on Drug Abuse, National Inst. of Health, Bethesda, MD (United States)

Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

OSTI ID:: 1183290

Report Number(s):: BNL--107778-2015-JA; KP1602010

Journal Information:: Journal of Labelled Compounds and Radiopharmaceuticals, Journal Name: Journal of Labelled Compounds and Radiopharmaceuticals Journal Issue: 3 Vol. 58; ISSN 0362-4803

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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Brain Monoamine Oxidase A Activity Predicts Trait Aggression Alia-Klein, N.; Goldstein, R. Z.; Kriplani, A. Journal of Neuroscience, Vol. 28, Issue 19 https://doi.org/10.1523/JNEUROSCI.0925-08.2008	journal	May 2008
Hydrogen Peroxide Produced by Mitochondrial Monoamine Oxidase Catalysis: Biological Implications Edmondson, Dale Current Pharmaceutical Design, Vol. 20, Issue 2 https://doi.org/10.2174/13816128113190990406	journal	January 2014
Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG Carter, S. F.; Scholl, M.; Almkvist, O. Journal of Nuclear Medicine, Vol. 53, Issue 1 https://doi.org/10.2967/jnumed.110.087031	journal	January 2012
Monoamine oxidase A and B substrates: probing the pathway for drug development Chajkowski-Scarry, Sarah; Rimoldi, John M. Future Medicinal Chemistry, Vol. 6, Issue 6 https://doi.org/10.4155/fmc.14.23	journal	April 2014
Evidence that the methylation state of the monoamine oxidase A ( MAOA ) gene predicts brain activity of MAO A enzyme in healthy men Shumay, Elena; Logan, Jean; Volkow, Nora D. Epigenetics, Vol. 7, Issue 10 https://doi.org/10.4161/epi.21976	journal	October 2012

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The monoamine oxidase inhibition properties of C6- and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives Marais, Lereze; Petzer, Anél; Petzer, Jacobus P. Molecular Diversity, Vol. 24, Issue 2 https://doi.org/10.1007/s11030-019-09960-5	journal	May 2019
Neuroinflammation in Neurodegenerative Disorders—a Review Schain, Martin; Kreisl, William Charles Current Neurology and Neuroscience Reports, Vol. 17, Issue 3 https://doi.org/10.1007/s11910-017-0733-2	journal	March 2017
Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity Doboszewska, Urszula; Wlaź, Piotr; Nowak, Gabriel Neural Plasticity, Vol. 2017 https://doi.org/10.1155/2017/3682752	journal	January 2017
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Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs Ramsay, Rona R.; Tipton, Keith F. Molecules https://doi.org/10.20944/preprints201707.0019.v1	journal	July 2017
Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration Ramsay, Rona R.; Majekova, Magdalena; Medina, Milagros Frontiers in Neuroscience, Vol. 10 https://doi.org/10.3389/fnins.2016.00375	journal	August 2016
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