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

Abstract

The dopamine D(2) receptor (D2R) is important in the mediation of addiction. [(123)I]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, [(123)I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [(123)I]IBZM for measuring D2R availability in mice. Pharmacokinetics of [(123)I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [(123)I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [(123)I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [(123)I]IBZM were compared. Specific binding of [(123)I]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 [(123)I]IBZM decreased significantly (-27.2%; n = 6; p = 0.046). Intravenous administration of [(123)I]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 [(123)I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [(123)I]IBZM. Imaging of D2R availability and endogenous dopamine release in mice is feasible using [(123)I]IBZM single pinhole SPECT. Using commercially produced [(123)I]IBZM, a dose of 40 MBq injected i.v. can be recommended.