Use of 11C-(+)-α-dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease

Abstract

This study evaluates the utility of (11)C-(+)-alpha -dihydrotetrabenazine ((11)C-(+)DTBZ) in the quantification of dopaminergic innervation by positron emission tomography (PET) in rat and monkey, two animal species used as animal models of Parkinson's disease. Healthy control animals (n = 10) and the effect of 6-hydroxidopamine (6-OHDA) neurotoxic were studied in rats. (18)F-DOPA PET studies and digital quantitative autoradiography were also carried out. Studies with Macaca fascicularis were performed in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) treated animals. In both species high quality images were generated in which clear uptake of (11)C-(+)DTBZ was found in the striatum. (11)C-(+)DTBZ uptake quantification was estimated by creating parametric images and binding potential (BP) calculation. BP in control rats was 1.10 +/- 0.16 (mean +/- standard deviation [SD], whereas 6-OHDA produced a decrease in the uptake depending on the lesion degree. Images obtained with (18)F-DOPA were not adequate for the analysis as they did not discriminate the stratum whereas digital quantitative autoradiography studies confirmed the high affinity of striatum by (11)C-(+)DTBZ. In monkeys, final BP values were 1.31 and 1.06 and MPTP treatment reduced uptake by 40 %. The quality of PET images and the decrease of uptake in 6-OHDA and MPTP lesions show that (11)C-(+)DTBZ is an adequate radiotracer for the study of dopaminergic innervation in these animal models.