Technetium-99m-Labeled Long Chain Fatty Acid Analogues Metabolized by β-Oxidation in the Heart

The development of 99mTc-labeled fatty acid analogues metabolized by β-oxidation in the myocardium constitutes an unsolved challenge. On the basis of our recent findings that [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was recognized as an aromatic compound and was metabo...

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Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 50; no. 3; pp. 543 - 549
Main Authors:	Uehara, Tomoya, Uemura, Tomoe, Hirabayashi, Seiji, Adachi, Sayaka, Odaka, Kenichi, Akizawa, Hiromichi, Magata, Yasuhiro, Irie, Toshiaki, Arano, Yasushi
Format:	Journal Article
Language:	English
Published:	Washington, DC American Chemical Society 08-02-2007
Subjects:	Animals Biological and medical sciences Biological Transport Contrast media. Radiopharmaceuticals Energy Metabolism Fatty Acids - chemistry In Vitro Techniques Iodobenzenes - pharmacokinetics Medical sciences Myocardium - metabolism Organotechnetium Compounds - chemical synthesis Organotechnetium Compounds - chemistry Organotechnetium Compounds - pharmacokinetics Oxidation-Reduction Pharmacology. Drug treatments Rats Technetium Tissue Distribution Heart Technetium complexes Transition element complexes Intravenous administration Rat Long chain Rodentia Bioavailability Metabolism Fatty acids Technetium Carbonyl Complexes Diagnostic agent Tissue Vertebrata Mammalia Scintigraphic agent Animal Distribution Technetium Organic compounds Hapto complex Oxidation Pharmacokinetics Radiopharmaceuticals
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Summary:	The development of 99mTc-labeled fatty acid analogues metabolized by β-oxidation in the myocardium constitutes an unsolved challenge. On the basis of our recent findings that [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was recognized as an aromatic compound and was metabolized as such in the body, [99mTc]cyclopentadienyltricarbonyltechnetium ([99mTc]CpTT) was conjugated at the ω-position of pentadecanoic acid to prepare [99mTc]CpTT-PA. When injected into rats, [99mTc]CpTT-PA exhibited the maximum myocardial accumulation and heart-to-blood ratio of 3.85 %ID/g at 1 min and 4.60 at 10 min postinjection, respectively. The metabolic study using isolated Langendorff perfused rat hearts demonstrated that approximately 67% of perfused [99mTc]CpTT-PA was incorporated and [99mTc]CpTT-propionic acid, the metabolite after six cycles of β-oxidation of [99mTc]CpTT-PA, was detected as the major radiometabolite in the perfusate and myocardium. These findings indicate that [99mTc]CpTT-PA was recognized, transported, and metabolized as a long chain fatty acid analogue for energy production in the myocardium.
Bibliography:	ark:/67375/TPS-LCLJ2BDL-7 istex:A459801F480A4B36C5EAA1640574957790906CF3 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm061017g