| Preliminary evaluation of 15-[18F]fluoro-3-oxa-pentadecanoate as a PET tracer of hepatic fatty acid oxidation. | |
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MedLine Citation:
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PMID: 11038005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The liver is an important site of fat oxidation. Abnormalities of hepatic mitochondrial fatty acid oxidation (HMFAO) are associated with obesity, type II diabetes, alcoholic hepatitis, and nonalcoholic steatohepatitis. Noninvasive assessment of HMFAO by PET has been impeded by the lack of a specific radiotracer. METHODS: No-carrier-added 15-[18F]fluoro-3-oxa-pentadecanoate (FOP) was synthesized and evaluated in living rats and isolated rat livers. RESULTS: FOP showed high uptake and slow clearance of radioactivity from livers in living rats. Inhibition of HMFAO by pretreatment of fasting rats with the carnitine palmitoyltransferase-I (CPT-I) inhibitor reduced the liver-to-blood ratio by 64%. In isolated rat livers, perfused in normoxic (95% O2) and hypoxic (15% O2) conditions with glucose (5 mmol/L) and palmitate (0.15 mmol/L), the externally measured kinetics of FOP showed reversible binding in tissue. The kinetics were adequately fit by a catenary 2-compartment model for estimation of tracer distribution volumes (DVs). The DVs of both compartments were found to correlate with fractional palmitate oxidation rate (FPOR) in experiments in normoxic and hypoxic conditions. The correlation was particularly strong for the slower second compartment (DV2 [mL/g dry weight] = 34.1 FPOR [mL/min/g dry weight] - 0.7, r = 0.89). Relatively small levels of diffusible metabolites of FOP were formed in vivo and in isolated rat liver. CONCLUSION: The selective uptake of FOP by liver and the high sensitivity of hepatic FOP DV to changes of HMFAO with CPT-I inhibition and hypoxia suggests potential usefulness for the 3-oxa fatty acid analog in assessments of hepatic mitochondrial oxidation of exogenous fatty acids with PET. These data emphasize that further studies are required to clarify the intracellular disposition of FOP in the liver and test its validity as a tracer of HMFAO over a broad range of conditions. |
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Authors:
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T R DeGrado; S Wang; D C Rockey |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of nuclear medicine : official publication, Society of Nuclear Medicine Volume: 41 ISSN: 0161-5505 ISO Abbreviation: J. Nucl. Med. Publication Date: 2000 Oct |
Date Detail:
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Created Date: 2000-11-09 Completed Date: 2000-11-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1727-36 Citation Subset: IM |
Affiliation:
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Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Fatty Acids / diagnostic use*, metabolism* Female Fluorine Radioisotopes / diagnostic use* Liver / metabolism*, radionuclide imaging Mitochondria, Liver / metabolism Oxidation-Reduction Radiopharmaceuticals / diagnostic use* Rats Rats, Sprague-Dawley Tissue Distribution Tomography, Emission-Computed* |
| Grant Support | |
ID/Acronym/Agency:
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HL-54882/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/15-fluoro-3-oxa-pentadecanoate; 0/Fatty Acids; 0/Fluorine Radioisotopes; 0/Radiopharmaceuticals |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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