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In the search for an in vivo marker of monoamine nerve terminal integrity, we investigated methoxytetrabenazine (MTBZ) as a tracer of the brain synaptic vesicular monoamine transporter (VMAT2). METHODS The biodistribution, metabolism and in vivo specificity of MTBZ binding were first evaluated in rodents and the human dosimetry was estimated. Subsequently, the human brain distribution of VMAT2 binding was determined in normal volunteers following administration of [11C]MTBZ. Brain regional time-activity curves were obtained, and parametric transport and binding images were calculated using arterial blood sampling and a two-compartment tracer kinetic model. RESULTS Regional rat brain localization of [3H]MTBZ 15 min postinjection was consistent with the known monoamine nerve terminal density, which demonstrated the highest activity in the striatum, lateral septum, substantia nigra pars compacta, the raphe nuclei and the locus coeruleus. At this time, chromatography revealed over 82% of brain activity, but less than 47% of plasma activity corresponded to authentic MTBZ. In vivo [11C]MTBZ binding in the mouse brain was inhibited by coinjection of excess unlabeled dihydrotetrabenazine. In humans [11C]MTBZ had high initial brain uptake and rapid clearance from all regions, with longest retention in areas of high VMAT2 concentration. Parametric quantification of VMAT2 density revealed the highest distribution volume in the putamen and caudate with lower values in cerebral cortex and cerebellum. CONCLUSIONS Carbon-11-MTBZ is a suitable ligand for PET quantification of the vesicular monoamine transporter in the human brain.
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
December 2000,
FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
January 2001,
Advances in neurology,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
December 2000,
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
October 2011,
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
March 1998,
Neurochemistry international,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
August 2004,
Experimental neurology,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
January 2022,
Acta physiologica (Oxford, England),
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
October 2017,
Journal of chemical neuroanatomy,
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
January 1998,
Advances in pharmacology (San Diego, Calif.),
T M Vander Borght, and
M R Kilbourn, and
R A Koeppe, and
J N DaSilva, and
J E Carey, and
D E Kuhl, and
K A Frey
November 2008,
Nuclear medicine and biology,
