Use of 11C-(+)-alpha-dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease
Collantes M, Peñuelas I, Alvarez-Erviti L, Blesa J, Martí-Climent JM, Quincoces G, Delgado M, Ecay M, Martínez A, Arbizu J, Rodríguez-Oroz MC, Obeso J, Richter JA.
Unidad de Investigación microPET, Centro de Investigación Médica Aplicada (CIMA)-Clínica Universitaria de Navarra, Pamplona, España.
his 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.
MATERIAL AND METHODS
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.
CITATION Rev Esp Med Nucl. 2008 Mar-Apr;27(2):103-11