Metabolism of technetium-99m-L,L-ethyl cysteinate dimer in rat and cynomolgus monkey tissue

Technetium-99m-L,L-ethyl cysteinate dimer (99mTc-ECD) is thought to be hydrolyzed in the brain by an enzyme and to be trapped as a hydrophilic product. We investigated the characteristics of the enzymatic system that metabolizes 99mTc-ECD.

In 50 mM phosphate buffer (pH 7.4), 99mTc-ECD was incubated with various concentrations of homogenates of rat tissues (blood, liver and brain) or cynomolgus monkey tissues (blood, liver, cerebral gray matter, cerebral white matter and cerebellar gray matter), and the metabolic rates were assessed. Inhibition studies were performed using diisopropyl fluorophosphate, eserine and p-chloromercuribenzoate as inhibitors. The metabolic rates in the brain homogenates of rat and monkey were measured at various levels of pH, ranging from 6.6 to 7.6. Technetium-99m-L,L-ethyl cysteinate dimer metabolism was also examined in the presence of purified enzymes.

In both species, the metabolic rate was high in liver tissue, intermediate in brain tissue and low in blood. The rate in cerebral gray matter of cynomolgus monkey was higher than those in rat brain, monkey cerebral white matter and monkey cerebellar gray matter. All substances used as inhibitors depressed 99mTc-ECD metabolism, and the response was different among tissues. Reduction in pH induced slight decreases in metabolic rate. Hydrophilic conversion of 99mTc-ECD was observed after incubation with porcine liver carboxylesterase.

These results support the hypothesis that the hydrophilic conversion of 99mTc-ECD is mediated by enzymes. It is also suggested that various enzymes catalyze the hydrolysis of 99mTc-ECD and that the enzymatic system that metabolizes 99mTc-ECD is different between tissues and between species.