8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver

Bioconjug Chem. 2004 Jan-Feb;15(1):121-7. doi: 10.1021/bc0341268.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caprylates / chemical synthesis*
  • Caprylates / pharmacokinetics*
  • Carbon Tetrachloride Poisoning / diagnostic imaging
  • Carbon Tetrachloride Poisoning / metabolism
  • Drug Stability
  • Fatty Acids / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • In Vitro Techniques
  • Indicators and Reagents
  • Liver / diagnostic imaging*
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Mice, Inbred ICR
  • Organotechnetium Compounds / chemical synthesis*
  • Organotechnetium Compounds / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Solvents
  • Tomography, Emission-Computed

Substances

  • 8-cyclopentadienyltricarbonyltechnetium-8-oxooctanoic acid
  • Caprylates
  • Fatty Acids
  • Indicators and Reagents
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Solvents