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Radioligands for Imaging Vesicular Monoamine Transporters

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PET and SPECT of Neurobiological Systems

Abstract

The vesicular monoamine transporter type 2 (VMAT2) is a protein specifically located in the membrane of neurotransmitter storage vesicles of monoaminergic neurons (dopamine, serotonin, norepinephrine, and histamine). The noninvasive in vivo imaging of this transporter has been utilized as a marker of the changes in monoaminergic innervation in human neurological diseases. Development of suitably radiolabeled compounds for in vivo imaging using positron emission tomography (PET) produced optimized carbon-11 ((+)-α-[11C]dihydrotetrabenazine, DTBZ) and fluorine-18 (9-(3-[18F]fluoropropyl)-dihydrotetrabenazine, AV-133) radioligands. Applications of VMAT2 radioligand imaging in numerous neurodegenerative diseases (e.g., Parkinson’s and related movement disorders, dementia with Lewy bodies) and psychiatric diseases (e.g., schizophrenia) and drug abuse have demonstrated that in vivo imaging of the VMAT2 provides a powerful tool to examine the progress and extent of changes of monoaminergic innervation in human disease conditions.

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Abbreviations

AD:

Alzheimer’s disease

AMPT:

Alpha-methyl-para-tyrosine

AV-133:

9-(3-fluoropropyl)-10-methoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-ol

DOPA:

3,4-dihydroxyphenylalanine

DTBZ:

Dihydrotetrabenazine: 9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-ol

fluoroDOPA:

6-fluoro-3,4-dihydroxyphenylalanine

MDMA:

3,4-methylenedioxy-N-methylamphetamine

MPTP:

1-methyl-4-phenyl-2,3,5,6-tetrahydropyridine

MPP+:

1-methyl-4-phenylpyridinium

MTBZ:

Methoxytetrabenazine

NMR:

Nuclear magnetic resonance

HD:

Huntington’s disease

LBD:

Lewy body disease

MSA:

Multiple system atrophy

OPCA:

Olivopontocerebellar atrophy

PD:

Parkinson’s disease

PDD:

Parkinson’s disease with dementia

PET:

Positron emission tomography

PSP:

Progressive supranuclear palsy

SPECT:

Single photon emission computed tomography

TBZ:

Tetrabenazine: 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-pyrido[2,1-a]isoquinolin-2-one

VMAT:

Vesicular monoamine transporter

VAChT:

Vesicular acetylcholine transporter

VGLUT:

Vesicular glutamate transporter

VGAT:

Vesicular GABA transporter

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Acknowledgements

The author would like to acknowledge the efforts of a large number of individuals at the University of Michigan and University of Pennsylvania who participated in the development of VMAT2 radioligands for human PET studies and in particular the advice, support, encouragement, and cooperation of Drs. Kirk Frey, Robert Koeppe, David Kuhl, and Hank Kung. This work was supported by a grant from the National Institutes of Health NS-15655.

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  1. Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Michael R. Kilbourn

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  1. Michael R. Kilbourn
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Correspondence to Michael R. Kilbourn .

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  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering and Information Technology, University of Applied Sciences Offenburg, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Molecular Neurobiology, Universtiy of Groningen, Groningen, The Netherlands

    Paul G.M. Luiten

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Kilbourn, M.R. (2014). Radioligands for Imaging Vesicular Monoamine Transporters. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Luiten, P. (eds) PET and SPECT of Neurobiological Systems. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-42014-6_27

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  • DOI: https://doi.org/10.1007/978-3-642-42014-6_27

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