Cerebral kinetics of the dopamine D₂ receptor ligand [¹²³I]IBZM in mice

Abstract 

Introduction

In vivo small animal imaging of the dopaminergic system is of great interest for basic and applied neurosciences, especially in transgenic mice. Small animal SPECT is particularly attractive because of its superior spatial resolution and tracer availability. We investigated the kinetics of the commercial dopamine D₂ receptor (DZR) ligand [¹²³I]IBZM in mice as a prerequisite for an appropriate design of translational SPECT imaging between mice and humans.

Methods

Cerebral kinetics of [¹²³I]IBZM under isoflurane anaesthesia were assessed by autoradiography in mice sacrificed at 30, 60, 120 and 200 min after iv injection. To explore the possible effects of isoflurane anaesthesia, an additional mice group was only anaesthetized for 20 min before being sacrificed at 140 min (putative time of single-scan SPECT analysis).

Results

Maximum [¹²³I]IBZM uptake in the striatum (D₂R-rich; 10.5±2.7 %ID/g) and cerebellum (D₂R-devoid; 2.4±0.7 %ID/g) was observed at 30 min after injection. Thereafter, [¹²³I]IBZM uptake decreased slowly in striatum and rapidly in the cerebellum (200 min: 5.3±1.9 and 0.4±0.2 %ID/g, respectively). The striatum-to-cerebellum (S/C) [¹²³I]IBZM uptake ratio increased from 4.6±1.2 at 30 min to 11.6±2.6 at 120 min. The S/C ratio at 200 min was highly variable (17.8±10.1), possibly indicating pseudo-equilibration in some animals. In mice, which were only anaesthetized between 120 and 140 min, a higher S/C ratio of 17.0±5.1 was observed.

Conclusions

The present study suggests that [¹²³I]IBZM is a suitable ligand for D₂R-SPECT in mice. Although a single-scan analysis may be a pragmatic semi-quantitative approach, tracer kinetic analyses on dynamic SPECT data should be pursued. The interfering effects of isoflurane anaesthesia need to be considered.

Keywords: Small animal imaging, SPECT, Dopamine D₂ receptor, [¹²³I]IBZM, Tracer kinetic analysis, Isoflurane anaesthesia