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-oxooetanoate and Na^99mTcO₄ 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 β-oxidation in the liver, and the radioactivity was retained longer in CCl₄-treated mice than in control mice, possibly due to impaired β-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 β-oxidation. The results suggested that this radiotracer might be of valuable use in the evaluation of fatty acid metabolism in the liver.