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

开发用于心肌成像的 Tc-99m 标记的长链脂肪酸衍生物。

• 批准号: 14570853
• 负责人: MAGATA Yasuhiro
• 金额: $ 2.24万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570853/
• 关键词: Branched Fatty Acid; Tc-99m; SPECT; Rat; Diagnosis; Radiopharmaceutical; Myocardial Function; Branched Fatty Acid; Tc-99m; SPECT; Rat; Diagnosis; Radiopharmaceutical; Myocardial Function

C-11 and I-123 labeled long chain fatty acid derivatives have been reported as useful radiopharjnaceuticals 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. Then, Tc-99m labeling and biodistribution studies were performed. 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). β-oxydative metabolite, short chain fatty acid … More derivative, Tc-99m-MAMA-BA was found in urine post-injection of Tc-99m-MAMA-HDA in normal rats. These results showed that Tc-99m-MAMA-HDA was recognized as a long chain fatty acid in the body. β-branched long chain fatty acid derivative, such as I-123-BMIPP, is used in clinical nuclear medicine. The radioactivity is accumulated in the heart by so-called metabolic trapping mechanism and this biological character is very useful for routine use. Then, synthesis of Tc-99m-MAMA-β-methyl-FA was carried out and an expected precursor, Trityl-MAMA-β-methyl-HDA was obtained with 14 steps. After Tc-99m labeling of this new compound, apreliminal biodistribution study was performed in normal mice. Although the radioactivity in the heart was not retained, further investigations may be needed. On the other hand, energy metabolism in the heart of Dahl model rats was investigated using an animal PET scanner and FDG. We established the experimental system and found usefulness of nuclear medicine technique in this field. Less

据报道，C-11和I-123标记为长链脂肪酸衍生物是有用的放射性放射性脂肪酸，用于估计心肌脂肪酸代谢。我们报告说，中链脂肪酸衍生物的 ^<99m> tc-mama-ha是通过肝脏中的β-氧化代谢的，在肝脏和妈妈配体中，可以与脂肪酸衍生物的欧米茄含量相连，作为带有TC-99M的螯合基团。基于这些发现，我们专注于开发标记为长链脂肪酸衍生物的TC-99M，反映了心肌中脂肪酸代谢。我们合成了一些长链脂肪酸（碳长度； 11（Mama-da），15（Mama-hda）），其中含有妈妈组为TC-99M的螯合组。然后，进行了TC-99M标记和生物分布研究。在使用小鼠的体内动物实验中，观察到TC-99M-MAMA-HDA的初始摄取更高的初始摄取。 I-125-ippa（p-碘 - 苯基五烷酸）的值是其中的一半。 β-氧化代谢物，短链脂肪酸…更衍生的TC-99M-MAMA-BA在正常大鼠的TC-99M-MAMA-HDA注射后发现了TC-99M-MAMA-BA。这些结果表明，TC-99M-MAMA-HDA被认为是体内的长链脂肪酸。 β支线的长链脂肪酸衍生物（例如I-123-BMIPP）用于临床核医学。放射性通过所谓的代谢诱捕机制积累在心脏中，这种生物学特征对于常规使用非常有用。然后，进行TC-99M-MAMA-β-甲基-FA的合成，并通过14个步骤获得了预期的前体Trityl-MAMA-β-甲基-HDA。在TC-99M对这种新化合物的标记后，在正常小鼠中进行了上型生物分布研究。尽管没有保留心脏的放射性，但仍需要进一步研究。另一方面，使用动物PET扫描仪和FDG研究了DAHL模型大鼠中心的能量代谢。我们建立了实验系统，发现核医学技术在该领域的有用性。较少的