Lee Byung Chul, Choe Yearn Seong, Chi Dae Yoon, Paik Jin-Young, Lee Kyung-Han, Choi Yong, Kim Byung-Tae
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
Bioconjug Chem. 2004 Jan-Feb;15(1):121-7. doi: 10.1021/bc0341268.
8-Cyclopentadienyltricarbonyl 99mTc 8-oxooctanoic acid (99mTc-CpTTOA; 1a) was synthesized for evaluation of medium chain fatty acid metabolism in the liver. 99mTc-CpTTOA was prepared in high radiochemical yield (50-63%) by a double ligand transfer reaction of methyl 8-ferrocenyl-8-oxooctanoate and Na99mTcO4 in the presence of CrCl3 and Cr(CO)6, followed by hydrolysis. This radiotracer was shown to be stable (>90% at 6 h) when incubated with human serum. Aqueous extraction of the radioactivity from the liver and blood samples of mice suggested that 99mTc-CpTTOA was mainly metabolized via beta-oxidation in the liver, and the radioactivity was retained longer in CCl4-treated mice than in control mice, possibly due to impaired beta-oxidation in the former. Planar images of rats injected with 99mTc-CpTTOA showed accumulation of the radioactivity in the liver, kidneys, and bladder with rapid hepatic clearance as a function of time. Analysis of the metabolites from the liver and urine samples of rats further supported that 99mTc-CpTTOA was metabolized to 4-cyclopentadienyltricarbonyl 99mTc 4-oxobutanoic acid (99mTc-CpTTBA; 1c) via beta-oxidation. The results suggested that this radiotracer might be of valuable use in the evaluation of fatty acid metabolism in the liver.
合成了8-环戊二烯基三羰基99mTc 8-氧代辛酸（99mTc-CpTTOA；1a）用于评估肝脏中中链脂肪酸代谢。通过8-二茂铁基-8-氧代辛酸甲酯与99mTcO4Na在CrCl3和Cr(CO)6存在下的双配体转移反应，然后水解，以高放射化学产率（50-63%）制备了99mTc-CpTTOA。该放射性示踪剂与人血清孵育时显示稳定（6小时时>90%）。从小鼠肝脏和血液样本中对放射性进行水相萃取表明，99mTc-CpTTOA主要在肝脏中通过β-氧化代谢，并且在CCl4处理的小鼠中放射性保留的时间比对照小鼠长，这可能是由于前者的β-氧化受损。注射99mTc-CpTTOA的大鼠的平面图像显示放射性在肝脏、肾脏和膀胱中积聚，肝脏清除迅速，呈时间函数关系。对大鼠肝脏和尿液样本中代谢物的分析进一步支持99mTc-CpTTOA通过β-氧化代谢为4-环戊二烯基三羰基99mTc 4-氧代丁酸（99mTc-CpTTBA；1c）。结果表明，这种放射性示踪剂可能在评估肝脏脂肪酸代谢方面具有重要价值。
