Effect of metabolic alterations on the accumulation of technetium-99m-labeled d,l-HMPAO in slices of rat cerebral cortex

It is widely recognized that the distribution of technetium-99m-labeled d,l-hexamethylpropylene amine oxime (^99mTc-HMPAO) in the brain is determined by the regional blood flow. However, other factors may affect this process including the metabolism of the brain tissue. To examine this possibility we studied the effects of metabolic alterations on ^99mTc-HMPAO uptake in rat brain cortex slices, with concurrent measurement of oxygen consumption (QO₂). ^99mTc-HMPAO uptake was determined by incubating slices of rat cerebral cortex at 37°C in Krebs-Ringer phosphate glucose medium containing ^99mTc-HMPAO with and without test substances. Differential gradients for ^99mTc activity between the tissue and the suspending medium (T/M ratio) were derived from the equation T/M[^99mTc] = counts per gram of tissue/counts per milliliter of medium. The QO₂ of the brain slices was measured using a biological oxygen monitor equipped with a polarographic oxygen probe. Inhibitors affecting oxidative phosphorylation caused parallel suppression of the T/M ratio and QO₂. Agents that uncouple oxidation from phosphorylation increased the QO₂ and decreased the T/M ratio. Incubation of slices at 22°C depressed the T/M ratio and QO₂. The presence of inhibitors of oxidative phosphorylation in the incubation medium increased the release of ^99mTc activity from slices that had been prelabeled with ^99mTc-HMPAO. These findings suggest that the altered metabolic status of the brain tissue modulates the kinetics and net accumulation of ^99mTc-HMPAO at the cellular level by either depressing uptake, increasing back-diffusion, or both.