SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

Purpose The dopamine D-2 receptor (D2R) is important in the mediation of addiction. [I-123]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [I-123]IBZM has not been used in mice SPECT studies. This study evaluates the use of [I-123]IBZM for measuring D2R availability in mice. Methods Pharmacokinetics of [I-123]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [I-123]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [I-123]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [I-123]IBZM were compared. Results Specific binding of [I-123]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [I-123]IBZM decreased significantly (-27.2%; n = 6; p = 0.046). Intravenous administration of [I-123]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [I-123]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [I-123]IBZM. Conclusions Imaging of D2R availability and endogenous dopamine release in mice is feasible using [I-123]IBZM single pinhole SPECT. Using commercially produced [I-123]IBZM, a dose of 40 MBq injected i.v. can be recommended.