Document Detail

Carbon-11 HOMADAM: a novel PET radiotracer for imaging serotonin transporters.
MedLine Citation:
PMID:  15820756     Owner:  NLM     Status:  MEDLINE    
Carbon-11-labeled N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine (HOMADAM) was synthesized as a new serotonin transporter (SERT) imaging agent. METHODS: Carbon-11 was introduced into HOMADAM by preparation of N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine followed by alkylation with carbon-11 iodomethane. Binding affinities of HOMADAM and the radiolabeling substrate, N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine, were determined in cDNA transfected cells expressing human SERT, dopamine transporters (DAT) and norepinephrine transporters NET using [3H]citalopram, [(125)I]RTI-55 and [3H]nisoxetine, respectively. MicroPET brain imaging was performed in monkeys. Arterial plasma metabolites of HOMADAM were analyzed in a rhesus monkey by high-performance liquid chromatography (HPLC). RESULTS: HOMADAM displayed high affinity for the SERT (Ki = 0.6 nM). N-methyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine displayed moderate affinity for the SERT (Ki = 15.11 nM). The affinities of HOMADAM for the DAT and NET were 2000- and 253-fold lower, respectively, than for the SERT. [11C]HOMADAM was prepared from [11C]iodomethane in approximately 25% radiochemical yield (decay-corrected to end of bombardment). MicroPET brain imaging studies in monkeys demonstrated that [11C]HOMADAM uptake was selectively localized in the midbrain, thalamus, pons, caudate, putamen and medulla. The midbrain-to-cerebellum, pons-to-cerebellum, thalamus-to-cerebellum and putamen-to-cerebellum ratios at 85 min were 4.2, 2.8, 2.3 and 2.0, respectively. HOMADAM binding achieved quasi-equilibrium at 45 min. Radioactivity in the SERT-rich regions of monkey brain was displaceable with R,S-citalopram. Radioactivity in the DAT-rich regions of monkey brain was not displaceable with the DAT ligand RTI-113. Radioactivity in the SERT-rich regions of monkey brain was displaceable with the R,S-reboxetine, a NET ligand with a high nanomolar affinity for SERT. Arterial plasma metabolites of HOMADAM were analyzed in a rhesus monkey by HPLC and displayed a single peak that corresponded to unmetabolized HOMADAM. CONCLUSION: HOMADAM is an excellent candidate for PET primate imaging of brain SERTs.
Nachwa Jarkas; John R Votaw; Ronald J Voll; Larry Williams; Vernon M Camp; Michael J Owens; David C Purselle; J Douglas Bremner; Clinton D Kilts; Charles B Nemeroff; Mark M Goodman
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  32     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-11     Completed Date:  2005-09-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  211-24     Citation Subset:  IM    
Center for Positron Emission Tomography, Emory University, Atlanta, GA 30322, USA.
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MeSH Terms
Benzylamines / chemistry,  diagnostic use*,  pharmacology*
Brain / metabolism*,  radionuclide imaging*
Cell Line
Kidney / metabolism*,  radionuclide imaging*
Macaca mulatta
Membrane Glycoproteins / metabolism*
Membrane Transport Proteins / metabolism*
Metabolic Clearance Rate
Nerve Tissue Proteins / metabolism*
Positron-Emission Tomography / methods*
Radiopharmaceuticals / chemical synthesis,  diagnostic use,  pharmacokinetics
Serotonin Plasma Membrane Transport Proteins
Tissue Distribution
Grant Support
R21 MH66622-01/MH/NIMH NIH HHS
Reg. No./Substance:
0/Benzylamines; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine; 0/Nerve Tissue Proteins; 0/Radiopharmaceuticals; 0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins

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