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两种新型放射性碘化 3-甲基支链脂肪酸心肌显像剂在大鼠心脏中的代谢评估。

Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents.

作者信息

Ambrose K R, Owen B A, Goodman M M, Knapp F F

出版信息

Eur J Nucl Med. 1987;12(10):486-91. doi: 10.1007/BF00620471.

DOI:10.1007/BF00620471
PMID:3569336
Abstract

The biological fate of two new radioiodinated 3-methyl-branched fatty acids has been evaluated in rat hearts following intravenous administration. Methyl-branching was introduced in [15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) to inhibit beta-oxidation. The goals of these studies were to correlate the effects of methyl-branching on the incorporation of these agents into the various fatty acid pools and subcellular distribution profiles, and to relate these data to the myocardial retention properties. The properties of BMIPP and DMIPP were compared with the 15-(p-iodophenyl)pentadecanoic acid straight-chain analogue (IPP). Differences in the heart retention of the analogues after intravenous administration in rats correlated with differences observed in subcellular distribution patterns. The dimethyl DMIPP analogue showed the longest retention and the highest association with the mitochondrial and microsomal fractions (34%, 38%) 30 min after injection. These data are in contrast to the rapid clearance of the straight-chain IPP analogue which showed much lower relative association with the mitochondria and microsomes (18%, 15%). The distribution patterns of each analogue in the various lipid pools appeared consistent with the expected capacity of the analogues to be metabolized by beta-oxidation. In contrast to the rapid oxidation of the straight-chain IPP analogue, the 3-monomethyl BMIPP analogue appeared to undergo slower oxidation and clearance, whereas the dimethyl-branched DMIPP analogue was apparently not catabolized by the myocardium. All three analogues showed some incorporation into triglycerides. The metabolism patterns of the branched analogues reported here may provide useful information in the description of the mechanisms by which BMIPP and DMIPP are retained in rat myocardium.

摘要

静脉注射后,在大鼠心脏中评估了两种新的放射性碘化3-甲基支链脂肪酸的生物学命运。在[15-(对碘苯基)-3-R,S-甲基十五烷酸(BMIPP)和15-(对碘苯基)-3,3-二甲基十五烷酸(DMIPP)中引入甲基支链以抑制β-氧化。这些研究的目的是关联甲基支链对这些试剂掺入各种脂肪酸池和亚细胞分布谱的影响,并将这些数据与心肌保留特性相关联。将BMIPP和DMIPP的特性与15-(对碘苯基)十五烷酸直链类似物(IPP)进行比较。大鼠静脉注射后类似物在心脏中的保留差异与亚细胞分布模式中观察到的差异相关。二甲基DMIPP类似物在注射后30分钟显示出最长的保留时间以及与线粒体和微粒体部分的最高关联度(34%,38%)。这些数据与直链IPP类似物的快速清除形成对比,后者与线粒体和微粒体的相对关联度要低得多(18%,15%)。每种类似物在各种脂质池中的分布模式似乎与类似物通过β-氧化代谢的预期能力一致。与直链IPP类似物的快速氧化相反,3-单甲基BMIPP类似物似乎经历较慢的氧化和清除,而二甲基支链的DMIPP类似物显然未被心肌分解代谢。所有三种类似物都显示出一些掺入甘油三酯的情况。此处报道的支链类似物的代谢模式可能为描述BMIPP和DMIPP在大鼠心肌中保留的机制提供有用信息。

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