18F-Labeled Octanoates as Potential Agents for Cerebral Fatty Acid Studies. The Influence of 4-Substitution and the Fluorine Position on Biodistribution

Fumi Nagatsugi, Fumiko Inoue, Shigeki Sasaki, Minoru Maeda

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

In order to understand the structural features that might lead to an in vivo radiotracer for studying cerebral fatty acid metabolism, 8-[18F]fluorooctanoate derivatives with methyl or gem-dimethyl branching at the C4 position have been prepared. 3-[18F]Fluoro- and 4-[18F]fluorooctanoic acid have also been synthesized for studying the influence of the fluorine position on the in vivo behavior of 18F-Iabeled octanoic acid analogs. Radiochemical synthesis was achieved by the nucleophilic displacement of a tosylate or mesylate precursor with [18F]fluoride ion. Tissue distribution studies in rats showed low cerebral uptakes of these 18F-labeled fatty acid analogs with poor brain-to-blood ratios. 3-[18F]Fluorooctanoic acid showed considerable defluorination, evident as a high bone activity level. The initial uptake of activity in the brain after injection of ethyl 8-[18F]fluoro-4-methyloctanoate and 4-[18F]-fluorooctanoic acid remained virtually unchanged over an extended time period, similar to that previously observed for the unbranched analogs, ethyl 8-[18F]fluorooctanoate and its free acid. In contrast, the 4-gem-dimethyl branched analog was rapidly and preferentially taken up by the liver. It was shown in the metabolite analysis that labeled metabolites produced from 8-[18F]fluoro-4-methyloctanoic acid were found in blood, and that they could enter the brain to a significant degree. Thus, the present studies showed that radioactivity retention in the brain in the case of the 4-methyl branched analog was mainly attributable to its radioactive metabolites.

元の言語英語
ページ(範囲)607-615
ページ数9
ジャーナルChemical and Pharmaceutical Bulletin
43
発行部数4
DOI
出版物ステータス出版済み - 1 1 1995

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Caprylates
Fluorine
Brain
Substitution reactions
Fatty Acids
Metabolites
Gems
Acids
Blood
Mesylates
Radioactivity
Tissue Distribution
Fluorides
Metabolism
Liver
Rats
Bone
Ions
Tissue
Derivatives

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

これを引用

18F-Labeled Octanoates as Potential Agents for Cerebral Fatty Acid Studies. The Influence of 4-Substitution and the Fluorine Position on Biodistribution. / Nagatsugi, Fumi; Inoue, Fumiko; Sasaki, Shigeki; Maeda, Minoru.

:: Chemical and Pharmaceutical Bulletin, 巻 43, 番号 4, 01.01.1995, p. 607-615.

研究成果: ジャーナルへの寄稿記事

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abstract = "In order to understand the structural features that might lead to an in vivo radiotracer for studying cerebral fatty acid metabolism, 8-[18F]fluorooctanoate derivatives with methyl or gem-dimethyl branching at the C4 position have been prepared. 3-[18F]Fluoro- and 4-[18F]fluorooctanoic acid have also been synthesized for studying the influence of the fluorine position on the in vivo behavior of 18F-Iabeled octanoic acid analogs. Radiochemical synthesis was achieved by the nucleophilic displacement of a tosylate or mesylate precursor with [18F]fluoride ion. Tissue distribution studies in rats showed low cerebral uptakes of these 18F-labeled fatty acid analogs with poor brain-to-blood ratios. 3-[18F]Fluorooctanoic acid showed considerable defluorination, evident as a high bone activity level. The initial uptake of activity in the brain after injection of ethyl 8-[18F]fluoro-4-methyloctanoate and 4-[18F]-fluorooctanoic acid remained virtually unchanged over an extended time period, similar to that previously observed for the unbranched analogs, ethyl 8-[18F]fluorooctanoate and its free acid. In contrast, the 4-gem-dimethyl branched analog was rapidly and preferentially taken up by the liver. It was shown in the metabolite analysis that labeled metabolites produced from 8-[18F]fluoro-4-methyloctanoic acid were found in blood, and that they could enter the brain to a significant degree. Thus, the present studies showed that radioactivity retention in the brain in the case of the 4-methyl branched analog was mainly attributable to its radioactive metabolites.",
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AB - In order to understand the structural features that might lead to an in vivo radiotracer for studying cerebral fatty acid metabolism, 8-[18F]fluorooctanoate derivatives with methyl or gem-dimethyl branching at the C4 position have been prepared. 3-[18F]Fluoro- and 4-[18F]fluorooctanoic acid have also been synthesized for studying the influence of the fluorine position on the in vivo behavior of 18F-Iabeled octanoic acid analogs. Radiochemical synthesis was achieved by the nucleophilic displacement of a tosylate or mesylate precursor with [18F]fluoride ion. Tissue distribution studies in rats showed low cerebral uptakes of these 18F-labeled fatty acid analogs with poor brain-to-blood ratios. 3-[18F]Fluorooctanoic acid showed considerable defluorination, evident as a high bone activity level. The initial uptake of activity in the brain after injection of ethyl 8-[18F]fluoro-4-methyloctanoate and 4-[18F]-fluorooctanoic acid remained virtually unchanged over an extended time period, similar to that previously observed for the unbranched analogs, ethyl 8-[18F]fluorooctanoate and its free acid. In contrast, the 4-gem-dimethyl branched analog was rapidly and preferentially taken up by the liver. It was shown in the metabolite analysis that labeled metabolites produced from 8-[18F]fluoro-4-methyloctanoic acid were found in blood, and that they could enter the brain to a significant degree. Thus, the present studies showed that radioactivity retention in the brain in the case of the 4-methyl branched analog was mainly attributable to its radioactive metabolites.

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