8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver.
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.
Lee
Byung Chul
BC
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
Choe
Yearn Seong
YS
Chi
Dae Yoon
DY
Paik
Jin-Young
JY
Lee
Kyung-Han
KH
Choi
Yong
Y
Kim
Byung-Tae
BT
D000818:Animals; D002210:Caprylates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002252:Carbon Tetrachloride Poisoning / Q000000981:diagnostic imaging / Q000378:metabolism; D004355:Drug Stability; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents; D014055:Tomography, Emission-Computed
C482338:8-cyclopentadienyltricarbonyltechnetium-8-oxooctanoic acid; D002210:Caprylates; D005227:Fatty Acids; D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012997:Solvents