THE POTENTIAL OF HIGH-RESOLUTION POSITRON EMISSION TOMOGRAPHY TO MONITOR STRIATAL DOPAMINERGIC FUNCTION IN RAT MODELS OF DISEASE

The use of a recently commissioned small-diameter, high-resolution pos itron emission tomograph (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using c erebellum as a reference tissue, compartmental modelling was;sed to ob tain individual estimates of striatal binding potential (defined as th e ratio of rate constants to and from the specifically bound compartme nt) for [C-11]raclopride (D-2 receptors), [C-11]SCH 23390 (D-1 recepto rs) and [C-11]RTI-121 (dopamine transporter). The coefficients of vari ation in control, anaesthetized rats were of the or der of 10%. Using two models of human disease, namely striatal injection of ibotenic aci d to produce postsynaptic cell loss as In Huntington's disease, and 6- hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease. marked reductions in binding potential were observed for the corresponding pre- or posts ynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factors such as sp ill over and partial volume negate absolute quantification of tissue r adioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques.