Chapter 3 - Quantification of Dopamine Receptors and Transporter in Rat Striatum Using a Small Animal PET Scanner

Abstract

This chapter reports on the use of a system to quantify specific binding of three positron-emitting tracers in rat striatum in vivo: [11C]SCH 23390 (D1 receptor antagonist), [11C]raclopride (D2 receptor antagonist), and the recently described dopamine transporter ligand [11C]RTI-121. A dedicated small-diameter positron emission tomography (PET) scanner has been used to quantify binding of three positron-emitting tracers in rat striatum in vivo: [11C]SCH 23390 (D1 receptor antagonist), [11C]-raclopride (D2 receptor antagonist), and the dopamine transporter ligand [11C]RTI-121. As the sizes of the striatal regions of interest used for analysis are of the same order as the dimensions of a detector element (3–4 mm), slight differences in the position of the rat within the scanner significantly affected the final images. Rats therefore were held in a perspex stereotaxic frame during scanning, thus abolishing movement and allowing precise positioning such that the striata were at the center of the field of view. Data are reported from a total of 31 previously untreated rats scanned over a period of 17 months. In addition, for each radioligand, groups of three rats were scanned after pretreatment with a blocking dose of the stable compound. Specific binding was quantified from the kinetic data using a reference tissue compartment model, with the cerebellum as an indirect input function. The results demonstrate that regional time-radioactivity data acquired using small animal positron emission tomography (PET) can provide reproducible and consistent quantitative information on pre- and postsynaptic dopaminergic function in rat striatum and that the system is sufficiently sensitive to allow the study of animal models of disease.