Technetium-99m-labeled medium-chain fatty acid analogues metabolized by beta-oxidation: Radiopharmaceutical for assessing liver function

External imaging of energy production activity of living cells with Tc-99m- labeled compounds is a challenging task requiring good design of Tc-99m-rad iopharmaceuticals. On the basis of our recent findings that C-11- and I-123 -labeled medium-chain fatty acids are useful for measuring beta-oxidation a ctivity of hepatocytes, we focused on development of Tc-99m-labeled medium- chain fatty acid analogues that reflect beta-oxidation activity of the live r. In the present study, monoamine-monoamide dithiol (MAMA) ligand and tria mido thiol (MAG) ligand were chosen as chelating groups because of the stab ility and size of their complexes with Tc-99m and their ease of synthesis. Each ligand was attached to the omega-position of hexanoic acid (MAMA-HA an d MAG-HA, respectively). In biodistribution studies, [Tc-99m]MAMA-HA showed high initial accumulation in the liver followed by clearance of the radioa ctivity in the urine. Analysis of the urine revealed [Tc-99m]MAMA-BA as the sole radiometabolite. Furthermore, when [Tc-99m]MAMA-HA was incubated with living liver slices, generation of [Tc-99m]MAMA-BA was observed. However, [Tc-99m]MAMA-HA remained intact when the compound was incubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of beta-oxidation. The findings in this study indicated that [Tc-99m]MAMA-HA was metabolized by beta-oxidation after incorporation into the liver. On the other hand, po or hepatic accumulation was observed after administration of [Tc-99m]MAG-HA .