In vivo binding of (+)-alpha-[H-3]dihydrotetrabenazine to the vesicular monoamine transporter of rat brain: bolus vs equilibrium studies

The regional rat brain distribution of (+)-alpha-[H-3]dihydrotetrabenazine was determined following (a) infusion to equilibrium between brain and blood or (b) bolus injection. Infusions provide for direct measurement of total distribution volumes. The free plus nonspecific distribution volume for the brain was determined using infusion of very low specific activity (+)-alpha-[H-3]dihydrotetrabenazine; specific distribution volumes, which represent specific radioligand binding, were then calculated as total minus the free + nonspecific distribution volume. Both total and specific distribution volumes correlated very well (r(2) > 0.99) with in vitro distributions of the vesicular monoamine transporter binding site. Bolus injection, and measurement of radioactivity at a single time point, also provided regional estimates of radioligand binding which correlated well (r(2) > 0.98) with in vitro values. The bolus method shows a small positive bias (+ 10-15%) in regions of high binding site concentrations. Both infusion and bolus injection methods give acceptable in vivo measures of(+)-alpha-[H-3]dihydrotetrabenazine binding to the vesicular monoamine transporter of rat brain. (C) 1997 Elsevier Science B.V.