| Validation of (99m)Tc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging: Part 2. Subcellular distribution. | |
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MedLine Citation:
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PMID: 19720296 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 36 ISSN: 1872-9614 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-01 Completed Date: 2009-12-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
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Languages: eng Pagination: 845-52 Citation Subset: IM |
Affiliation:
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Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany. peter_mirtschink@web.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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chemistry Animals Biological Transport / drug effects Carnitine O-Palmitoyltransferase / antagonists & inhibitors, metabolism Cattle Enzyme Inhibitors / pharmacology Epoxy Compounds / pharmacology Fatty Acid-Binding Proteins / metabolism Fatty Acids / chemical synthesis, chemistry*, diagnostic use, metabolism* Female Heart / drug effects, radionuclide imaging Intracellular Space / drug effects, metabolism* Isotope Labeling Male Mice Mitochondria / metabolism Myocardial Perfusion Imaging* Myocardium / cytology*, metabolism* Organotechnetium Compounds / chemistry* Rats Reproducibility of Results |
| Chemical | |
Reg. No./Substance:
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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 2.3.1.21/Carnitine O-Palmitoyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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