99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic acid: a potential radiotracer for evaluation of fatty acid metabolism

Bioconjug Chem. 2007 Jul-Aug;18(4):1332-7. doi: 10.1021/bc060299w. Epub 2007 May 16.

Abstract

99mTc(CO)3-15-[N-(Acetyloxy)-2-picolylamino]pentadecanoic acid (1a) was prepared by incorporating [99mTc(CO)3]+ into 15-[N-(hydroxycarbonylmethyl)-2-picolylamino]pentadecanoic acid (2a). The overall radiochemical yield of 1a after HPLC purification was 60-63%. Radiotracer 1a was found to be chemically stable when incubated in human plasma for 4 h at 37 degrees C. Tissue distribution studies showed that high radioactivity accumulated in the heart with rapid clearance. The maximum heart-to-blood uptake ratio was 1.87 at 5 min after a tail-vein injection. Radioactive metabolites were analyzed in urine samples of mice and corresponded to a 9.3:1 ratio of 99mTc(CO)3-5-[N-(acetyloxy)-2-picolylamino]pentanoic acid (1b) to 99mTc(CO)3-3-[N-(acetyloxy)-2-picolylamino]propionic acid (1c), indicating that 1a is mainly metabolized to 1b via beta-oxidation in the body. These results suggest that 1a is a promising radiotracer for evaluation of fatty acid metabolism in myocardium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acids / blood
  • Fatty Acids / chemistry*
  • Fatty Acids / pharmacokinetics*
  • Fatty Acids / urine
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardium / metabolism
  • Radioactive Tracers*
  • Technetium / blood
  • Technetium / chemistry*
  • Technetium / pharmacokinetics*
  • Technetium / urine
  • Tissue Distribution

Substances

  • Fatty Acids
  • Radioactive Tracers
  • Technetium
  • pentadecanoic acid