Document Detail

Characterization of [11C]tetrabenazine as an in vivo radioligand for the vesicular monoamine transporter.
MedLine Citation:
PMID:  9234277     Owner:  NLM     Status:  MEDLINE    
[11C]Tetrabenazine ([11C]TBZ) is a new in vivo radioligand for positron emission tomographic (PET) imaging of vesicular monoamine transporters. The in vivo distribution, metabolism and pharmacological specificity of [11C]TBZ has been determined in rodents. Regional mouse brain retention of [11C]TBZ is highest in brain regions with greatest monoaminergic innervation (striatum, hypothalamus) and can be reduced with ligands for the monoamine vesicular transporter (TBZ, ketanserin) but not haloperidol, a dopamine D2 receptor antagonist. Chromatographic analysis of rat blood demonstrated rapid metabolism of [11C]TBZ to radiolabeled metabolites (alpha- and beta -[11C]dihydrotetrabenazine) resulting from reduction of the 2-keto group. These metabolites, as well as a third potential metabolite, 9-O-desmethylTBZ, have been synthesized in unlabeled form and all three were shown to be capable of greatly reducing in vivo accumulation of [11C]TBZ in mouse striatum and hypothalamus. Whole body biodistribution of radioactivity after [11C]TBZ injection was determined in rats, and the data used to calculate the expected human dosimetry from this radiotracer. These studies demonstrated that [11C]TBZ can be safely administered for in vivo PET imaging and semi-quantitative determination of vesicular monoamine transporters in living human brain, but quantitative pharmacokinetic modeling of radioactivity distribution will be complicated by the presence of pharmacologically active metabolites.
J N DaSilva; J E Carey; P S Sherman; T J Pisani; M R Kilbourn
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  21     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1997-09-25     Completed Date:  1997-09-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  151-6     Citation Subset:  IM    
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
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MeSH Terms
Binding, Competitive
Biogenic Monoamines / metabolism*
Biological Transport / physiology
Carbon Radioisotopes / diagnostic use
Membrane Glycoproteins / metabolism*
Nerve Degeneration / physiology
Radiation Dosage
Radioligand Assay
Rats, Sprague-Dawley
Tetrabenazine / metabolism*
Tissue Distribution
Grant Support
Reg. No./Substance:
0/Biogenic Monoamines; 0/Carbon Radioisotopes; 0/Membrane Glycoproteins; 58-46-8/Tetrabenazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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