Journal Article

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

Booij, Jan, Beekman, Freek, de Bruin, Kora, Jongen, Cynthia

2008

Overview

Purpose 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. Methods 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. Results 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. Conclusions 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.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Addictions / Alcohols - toxicity / Amphetamine - pharmacology / Anesthesia / Animals / Binding sites / Brain / Cardiology / Dopamine - metabolism / Imaging / Injections, Intraperitoneal / Injections, Intravenous / Iodobenzenes - administration & dosage / Iodobenzenes - pharmacokinetics / Longitudinal Studies / Male / Medicine / Medicine & Public Health / Mice / Neurotransmitters / Nuclear Medicine / Oncology / Original Article / Orthopedics / Radiology / Receptors, Dopamine D2 - metabolism / Reproducibility of Results / Rodents / Scientific imaging / Time Factors / Tomography, Emission-Computed, Single-Photon