PRESYNAPTIC MONOAMINERGIC VESICLES IN PARKINSONS-DISEASE AND NORMAL AGING

We present development and human application of a method for determini ng the regional cerebral density of the type 2 vesicular monoamine tra nsporter (VMAT2) using positron emission tomography (PET) and [C-11] d ihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory r egulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [C-11]DTBZ transport (K-1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) f rom the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DV with a dvancing age, corresponding to losses of 0.77% per year in specific VM AT2 binding. Parkinson's disease (PD) patients had reduction in specif ic DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). Th ere was no overlap of lowest specific putamen DTBZ DV between individu al elderly controls and PD patients. The present results indicate the suitability of [C-11]DTBZ PET for objective quantification of nigrostr iatal integrity, including evaluation of PD progression and its possib le therapeutic modification.