Quantification of dopamine d2 receptor density and apparent affinity can be used to longitudinally assess transient striatal variations during adolescence using [11c]raclopride pet imaging

Background Transient increases in striatal dopamine D2 receptors occur during adolescence in rats, correlating with a developmental epoch where synaptic pruning occurs. Alteration of these processes with external stresses during adolescence may lead to affective disorders later in life. Longitudinal PET imaging with [11C]raclopride using a partial saturation design allows assessment of density (Bavail) and affinity changes (appKd) to map neurodevelopmental changes in D2 expression, which necessitates a significant level of receptors occupancy during the PET study. Aims Validate that repeated transient partial saturation of D2 receptors does not bias measures of D2 Bavail and appKd assessed using PET/CT imaging with [11C]raclopride. Methods Three cohorts of male Sprague-Dawley rats (n=6-7/group) underwent a single session of PET/CT imaging (INVEON, Siemens, USA) with [11C]raclopride (5 nmol injected i.v.) as naïve or after repeated partial saturation of D2 receptors: Cohort A received 5nmol raclopride (i.v) weekly from PND35 (postnatal day) to PND96 with PET imaging session at PND96, cohort B was scanned at PND96; Cohort C was scanned at PND35 Datasets were reconstructed (2D-FBP), coregistered with CT and time-activity data extracted using age matched atlas-based volumes of interest (striatum, cerebellum). in vivo receptor density and appKd were derived using kinetic modelling (comparisons used 1-way ANOVA follow by post hoc test). Results Expected differences in Bavail and appKd were seen between the adolescent (PND35) and the adult (PND96) cohorts, corresponding with increases in D2 receptor consistently reported in the literature using post mortem methods. No significant difference was observed in both Bavail and appKd in cohort A, exposed to repeated D2 partial saturation, compared to the naïve cohort B. Conclusion Longitudinal quantification of dopamine D2 receptor density and apparent affinity in vivo using [11C]raclopride PET imaging with partial saturation can be used to map changes in adolescent and adult rats.

Keywords

Dopamine, Receptors, Adolescents, Positron computed tomography, Rats, CAT scanning, Injection, Density, Data

Citation

Callaghan, P., Sobbi, P. F., Safavi-Naeini, M., Wimberley, C., Davis, E., Zahra, D., Arthur, A., Rahardjo, G., Perkins, G., Pascali, G., Reilhac-Laborde, A., & Gregoire, M. C. (2017). Quantification of dopamine d2 receptor density and apparent affinity can be used to longitudinally assess transient striatal variations during adolescence using [11c]raclopride pet imaging. Presentation to the 47th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine Hobart, Tasmania, 21–23 Apr 2017. In Internal Medicine Journal, 47(S1), 5-23. doi:10.1111/imj.13422