EFFECT OF METABOLIC ALTERATIONS ON THE ACCUMULATION OF TC-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 (Tc-99m-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 Tc-99m-HMPAO uptake in rat brain cortex slices, with concurrent measurement of oxygen consumption (QO(2)). Tc-99m-HMPAO uptake was determined by incubating slices of rat cerebral cortex at 37 degrees 0 in Krebs-Ringer phosphate glucose medium containing Tc-99m-HMPAO with and without test substances. Differential gradients for Tc-99m activity between the tissue and the suspending medium (T/M ratio) were derived from the equation T/M[Tc-99m] = counts per gram of tissue/counts per milliliter of medium. The QO(2) 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 QO(2). Agents that uncouple oxidation from phosphorylation increased the QO(2) and decreased the T/M ratio. Incubation of slices at 22 degrees 0 depressed the T/M ratio and QO(2). The presence of inhibitors of oxidative phosphorylation in the incubation medium increased the release of Tc-99m activity from slices that had been prelabeled with Tc-99m-HMPAO. These findings suggest that the altered metabolic status of the brain tissue modulates the kinetics and net accumulation of Tc-99m-HMPAO at the cellular level by either depressing uptake, increasing back-diffusion, or both.