文章基本信息

标题：Cu-Pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), a Metal Complex with Selective NADH-Dependent Reduction by Complex I in Brain Mitochondria : A Potential Radiopharmaceutical for Mitochondria-Functional Imaging with Positron Emission Tomography (PET)
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作者：Hideyuki TANIUCHI ; Yasuhisa FUJIBAYASHI ; Hidehiko OKAZAWA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1995
卷号：18
期号：8
页码：1126-1129
DOI：10.1248/bpb.18.1126
出版社：The Pharmaceutical Society of Japan
摘要：The reductive retention mechanism of copper (II)-pyruvaldehyde-bis (N⁴-methylthiosemicarbazone) (Cu-PTSM), a generator-produced positron-emitting ⁶²Cu-labeled radiopharmaceutical, was studied with non-radioactive and radioactive copper. Changes in the chemical form of Cu-PTSM were detected by electron spin resonance spectrometry (ESR) with cold copper. The effects of electron transport chain inhibitors on the reduction of Cu-PTSM were also examined. Rotenone and antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6-and 1.4-fold, respectively, compared with untreated controls, while thenoyltrifluoroacetone (TTFA) had no effect on the reduction. These results were confirmed with radioactive copper. Furthermore, this reduction of Cu-PTSM was dependent on the protein concentration of mouse brain submitochondrial particle (SMP) with 1mM NADH (0 mg-protein/ml : 1.8±2.5%, 8mg-protein/ml : 69.0±5.5%, each value was % of reduced Cu). Similarly, this reduction depended on NADH concentration at a fixed concentration of SMP (8mg-protein/ml). These results indicated that the electron transport chain, especially complex I, participated in the reduction of Cu-PTSM in brain mitochondria, and this suggested that Cu-PTSM has the potential to act as a functional imaging agent for diagnosis of the electron transport chain.
关键词：^ Cu-PTSM;brain;complex I;mitochondrial function;positron emission tomography imaging agent