| Validation of (99m)Tc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging: Part 1: myocardial extraction and biodistribution. | |
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MedLine Citation:
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PMID: 19720295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: (13)C, (18)F and (123)I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [(99m)Tc]-labeled "4+1" FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives. METHODS: Studies were performed with isolated perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with a FAT/CD36 deficiency, as well as with heart type FA binding protein knockout mice (H-FABP)(-/-) and H-FABP(+/+). Eight 4+1-(99m)Tc-FA were applied for 3 min followed by 1-min washout. A mathematical model was used to analyze FA dynamics and binding to proteins. Whole-body distribution was studied in rats with and without Tween 80. In vitro fractionation studies with [(99m)Tc]-FA assessed red blood cell uptake as well as association with plasma lipoproteins very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). RESULTS: Myocardial extraction was 19.0-33.0% of the infused dose in isolated WKY and 15.2-26.4% in SHR hearts. However, H-FABP(-/-) showed a marked reduction of tracer extraction [2.8+/-0.6%ID (percent injected dose) vs. 17+/-2%ID P<.001]. Uptake in red blood cells (<1.2%ID) and incorporation into lipoproteins were negligible. Incubation of (99m)Tc-FA with albumin reduced ventricular extraction (P<.001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies. CONCLUSIONS: Myocardial uptake of [(99m)Tc]-FA 4+1 derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP. |
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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: 833-43 Citation Subset: IM |
Affiliation:
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Institute of Physiology, Technical University Dresden, 01307 Dresden, Germany. peter_mirtschink@web.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD36 / metabolism Biological Transport / drug effects Cattle Cytosol / metabolism Erythrocytes / metabolism Fatty Acid-Binding Proteins / metabolism Fatty Acids / chemistry, diagnostic use, metabolism*, pharmacokinetics* Female Heart / drug effects, physiology, radionuclide imaging Heart Ventricles / metabolism Hemodynamics Humans Intracellular Space / metabolism Isotope Labeling Lipid Metabolism Male Mice Models, Biological Myocardial Perfusion Imaging* Myocardium / cytology, metabolism* Organotechnetium Compounds / chemistry* Rats Reproducibility of Results Serum Albumin, Bovine / pharmacology Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD36; 0/Fabp3 protein, mouse; 0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/Organotechnetium Compounds; 0/Serum Albumin, Bovine |
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