8-Cyclopentadienyltricarbonyl super(99m)Tc 8-Oxooctanoic Acid: A Novel Radiotracer for Evaluation of Medium Chain Fatty Acid Metabolism in the Liver

• Published in: Bioconjugate chemistry 2004-01, Vol.15 (1), p.121-127
• Main Authors: Lee, B C, Choe, Y S, Chi, D Y, Paik, J-Y, Lee, K-H, Choi, Y, Kim, B-T
• Format: Article
• Language: English
• Subjects: methyl 8-ferrocenyl-8-oxooctanoate
• ISSN: 1043-1802
• DOI: 10.1021/bc0341268

8-Cyclopentadienyltricarbonyl super(99m)Tc 8-oxooctanoic acid ( super(99m)Tc-CpTTOA; 1a) was synthesized for evaluation of medium chain fatty acid metabolism in the liver. super(99m)Tc-CpTTOA was prepared in high radiochemical yield (50-63%) by a double ligand transfer reaction of methyl 8-ferrocenyl-8-oxooctanoate and Na super(99m)TcO sub(4) in the presence of CrCl sub(3) and Cr(CO) sub(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 super(99m)Tc-CpTTOA was mainly metabolized via beta -oxidation in the liver, and the radioactivity was retained longer in CCl sub(4)-treated mice than in control mice, possibly due to impaired beta -oxidation in the former. Planar images of rats injected with super(99m)Tc-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 super(99m)Tc-CpTTOA was metabolized to 4-cyclopentadienyltricarbonyl super(99m)Tc 4-oxobutanoic acid ( super(99m)Tc-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.