[³H]Methotrexate Loss from the Rat Brain following Enhanced Uptake by Osmotic Opening of the Blood-Brain Barrier

Right brain regions of anesthetized rats were loaded with [3,5,7-³H]methotrexate (³H]MTX) or with [¹⁴C]sucrose by infusing the tracers into the right carotid artery, after the blood-brain barrier had been opened by right carotid infusion of a hypertonic arabinose solution. During the 6 hr following the procedure, the [³H]MTX concentration in 7 right-sided brain regions, when normalized to the plasma concentration integral during tracer infusion, fell, with an average half-time of 4.8 hr as compared to less than 20 min for the initial rate of toss of [¹⁴C]sucrose. Right-left brain concentration differences 3 hr after treatment were statistically significant (p < 0.05) for [³H]MTX but not for [¹⁴C]sucrose. The results indicate that intracerebral [³H]MTX is lost more slowly than is intracerebral [¹⁴C]sucrose, possibly because [³H]MTX enters brain cells, whereas [¹⁴C]sucrose remains largely extracellular.