Document Detail


Ex vivo and in vivo evaluation of the norepinephrine transporter ligand [11C]MRB for brown adipose tissue imaging.
MedLine Citation:
PMID:  22595487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: It has been suggested that brown adipose tissue (BAT) in humans may play a role in energy balance and obesity. We conducted ex vivo and in vivo evaluation using [(11)C]MRB, a highly selective NET (norepinephrine transporter) ligand for BAT imaging at room temperature, which is not achievable with [(18)F]FDG.
METHODS: PET images of male Sprague-Dawley rats with [(18)F]FDG and [(11)C]MRB were compared. Relative [(18)F]FDG or [(11)C]MRB retention at 20, 40 and 60 min post-injection was quantified on awake rats after exposing to cold (4°C for 4h) or remaining at room temperature. Rats pretreated with unlabeled MRB or nisoxetine 30 min before [(11)C]MRB injection were also assessed. The [(11)C]MRB metabolite profile in BAT was evaluated.
RESULTS: PET imaging demonstrated intense [(11)C]MRB uptake (SUV of 2.9 to 3.3) in the interscapular BAT of both room temperature and cold-exposed rats and this uptake was significantly diminished by pretreatment with unlabeled MRB; in contrast, [(18)F]FDG in BAT was only detected in rats treated with cold. Ex vivo results were concordant with the imaging findings; i.e. the uptake of [(11)C]MRB in BAT was 3 times higher than that of [(18)F]FDG at room temperature (P=0.009), and the significant cold-stimulated uptake in BAT with [(18)F]FDG (10-fold, P=0.001) was not observed with [(11)C]MRB (P=0.082). HPLC analysis revealed 94%-99% of total radioactivity in BAT represented unchanged [(11)C]MRB.
CONCLUSIONS: Our study demonstrates that BAT could be specifically labeled with [(11)C]MRB at room temperature and under cold conditions, supporting a NET-PET strategy for imaging BAT in humans under basal conditions.
Authors:
Shu-fei Lin; Xiaoning Fan; Catherine Weikart Yeckel; David Weinzimmer; Tim Mulnix; Jean-Dominique Gallezot; Richard E Carson; Robert S Sherwin; Yu-Shin Ding
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Publication Detail:
Type:  Journal Article     Date:  2012-05-16
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  39     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2013-02-12     Revised Date:  2014-06-30    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1081-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue, Brown / metabolism,  radionuclide imaging*
Animals
Fluoxetine / analogs & derivatives,  metabolism,  pharmacology
Ligands
Male
Morpholines / diagnostic use*,  metabolism*,  pharmacokinetics
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors,  metabolism*
Positron-Emission Tomography / methods*
Rats
Rats, Sprague-Dawley
Wakefulness
Grant Support
ID/Acronym/Agency:
R01 DK020495/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; 0/Morpholines; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/O-methyl reboxetine; 01K63SUP8D/Fluoxetine; 17NV064B2D/nisoxetine
Comments/Corrections

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