Document Detail

Validation of (99m)Tc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging: Part 2. Subcellular distribution.
MedLine Citation:
PMID:  19720296     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [(99m)Tc]"4+1" FA. METHODS: Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP(-/-) mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography. RESULTS: The largest fraction of tissue radioactivity was associated with cytosol [79.69+/-8.88% of infused dose]. About 9.07+/-0.95% and 3.43+/-1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [(123)I]-labeled 15-(p-iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction (P<.001). No metabolic product of [(99m)Tc]"4+1" FA could be detected in any isolated heart. CONCLUSIONS: Myocardial [(99m)Tc]"4+1" FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.
Peter Mirtschink; Sebastian N Stehr; Martin Walther; Jens Pietzsch; Ralf Bergmann; Hans-J??rgen Pietzsch; Johannes Weichsel; Annette Pexa; Peter Dieterich; Gerd Wunderlich; Bert Binas; Joachim Kropp; Andreas Deussen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  36     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-01     Completed Date:  2009-12-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  845-52     Citation Subset:  IM    
Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany.
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MeSH Terms
Amides / chemistry
Biological Transport / drug effects
Carnitine O-Palmitoyltransferase / antagonists & inhibitors,  metabolism
Enzyme Inhibitors / pharmacology
Epoxy Compounds / pharmacology
Fatty Acid-Binding Proteins / metabolism
Fatty Acids / chemical synthesis,  chemistry*,  diagnostic use,  metabolism*
Heart / drug effects,  radionuclide imaging
Intracellular Space / drug effects,  metabolism*
Isotope Labeling
Mitochondria / metabolism
Myocardial Perfusion Imaging*
Myocardium / cytology*,  metabolism*
Organotechnetium Compounds / chemistry*
Reproducibility of Results
Reg. No./Substance:
0/Amides; 0/Enzyme Inhibitors; 0/Epoxy Compounds; 0/Fabp3 protein, mouse; 0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/Organotechnetium Compounds; 82258-36-4/etomoxir; EC O-Palmitoyltransferase

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