External imaging of energy production activity of living cells with
99mTc-labeled compounds is achallenging task requiring good design of
99mTc-radiopharmaceuticals. On the basis of our recentfindings that
11C- and
123I-labeled medium-chain fatty acids are useful for measuring
-oxidationactivity of hepatocytes, we focused on development of
99mTc-labeled medium-chain fatty acid analoguesthat reflect
-oxidation activity of the liver. In the present study, monoamine-monoamide dithiol(MAMA) ligand and triamido thiol (MAG) ligand were chosen as chelating groups because of thestability and size of their complexes with
99mTc and their ease of synthesis. Each ligand was attachedto the
-position of hexanoic acid (MAMA-HA and MAG-HA, respectively). In biodistribution studies,[
99mTc]MAMA-HA showed high initial accumulation in the liver followed by clearance of theradioactivity in the urine. Analysis of the urine revealed [
99mTc]MAMA-BA as the sole radiometabolite.Furthermore, when [
99mTc]MAMA-HA was incubated with living liver slices, generation of [
99mTc]MAMA-BA was observed. However, [
99mTc]MAMA-HA remained intact when the compound wasincubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of
-oxidation. The findingsin this study indicated that [
99mTc]MAMA-HA was metabolized by
-oxidation after incorporation intothe liver. On the other hand, poor hepatic accumulation was observed after administration of [
99mTc]MAG-HA.