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Development of Tc-99m labeled long chain fatty acid derivative for myocardial imaging

用于心肌成像的Tc-99m标记长链脂肪酸衍生物的开发

基本信息

批准号：
12670866
负责人：
MAGATA Yasuhiro
金额：
$ 2.05万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670866/
关键词：
Long chain fatty acid Tc-99m SPECT RAT Myocardium Radiopharmaceuticals Diagnosis

项目摘要

C-11 and I-123 labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for estimation of myocardial fatty acid metabolism. We have reported that ^<99m>Tc-MAMA-HA, middle chain fatty acid derivative, is metabolized by beta-oxidation in a liver and MAMA ligand is useful to attach to the omega-position of fatty acid derivative as a chelating group with Tc-99m. Based on these findings, we focused on developing Tc-99m labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium.We synthesized some long chain fatty acids (carbon length ; 11 (MAMA-DA), 15 (MAMA-HDA)) containing MAMA group in its molecule as a chelating group with Tc-99m. After the synthesis, Tc-99m labeling was performed by ligand-exchange reaction with Tc-99m-pertechnetate reduced by Sn(II) glucoheptonate in diluted ethanol solution and purified with HPLC system. Tc-99m labeled long chain fatty acid derivatives were obtained with radiochemical yield of >70 % and radiochemical purity of >95 %.A Higher initial uptake of Tc-99m-MAMA-HDA was observed in in vivo animal experiments using mice. The value was half of that by I-125-IPPA (p-iodo-phenyl pentadecanoic acid). Beta oxidation of Tc-99m-MAMA-HDA was investigated using primary cell culture of adult rats myocardium as a preliminary study. The metabolites were analyzed by radio TLC. It was indicated that Tc-99m-MAMA-HDA was metabolized to a short chain fatty acid derivative by the myocardium in vitro.In conclusion, Tc-99m-MAMA-HDA may be recognized as a long chain fatty acid in the myocardium although further examination are required. This Tc-99m labeled compound is useful to evaluate fatty acid metabolism in the myocardium.

据报道，C-11和I-123标记的长链脂肪酸衍生物是用于估计心肌脂肪酸代谢的有用的放射性药物。我们已经报道了<99m>，中链脂肪酸衍生物-在此基础上，我们合成了一些长链脂肪酸（碳长11（MAMA-DA），15（MAMA-HDA）），分子中含有MAMA基团作为Tc-99 m的螯合基团。合成完成后，在稀乙醇溶液中用葡庚糖酸Sn（II）还原Tc-99 m-高锝酸盐，通过配体交换反应进行Tc-99 m标记，并用HPLC系统纯化。用~（99 m）Tc标记长链脂肪酸衍生物，放化产率> 70%，放化纯度> 95%，在小鼠体内实验中观察到较高的~（99 m-MAMA-HDA）初始摄取。该值是I-125-IPPA（对碘苯基十五烷酸）的一半。用成年大鼠心肌原代细胞培养法研究了Tc-99 m-MAMA-HDA的β氧化作用。通过放射性TLC分析代谢物。结果表明，Tc-99 m-MAMA-HDA在离体心肌中被代谢为短链脂肪酸衍生物，Tc-99 m-MAMA-HDA在心肌中可能是长链脂肪酸，但尚需进一步研究。这种Tc-99 m标记的化合物可用于评价心肌中的脂肪酸代谢。