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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The dopamine D2 receptor (D2R) is important in the mediation of addiction. [123I]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, [123I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [123I]IBZM for measuring D2R availability in mice.

Methods

Pharmacokinetics of [123I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [123I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [123I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [123I]IBZM were compared.

Results

Specific binding of [123I]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 [123I]IBZM decreased significantly (−27.2%; n = 6; p = 0.046). Intravenous administration of [123I]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 [123I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [123I]IBZM.

Conclusions

Imaging of D2R availability and endogenous dopamine release in mice is feasible using [123I]IBZM single pinhole SPECT. Using commercially produced [123I]IBZM, a dose of 40 MBq injected i.v. can be recommended.

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Acknowledgments

We would like to thank Dr. Louk J.M.J. Vanderschuren for his critical reading of the manuscript and his useful comments.

The research was funded by a grant from the University Medical Center Utrecht and the Academic Medical Center.

The experiments comply with the laws of the Netherlands and were approved by the Committee for Animal Care of the Academic Medical Center. The authors have no conflict of interest.

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Authors and Affiliations

  1. Image Sciences Institute, University Medical Center Utrecht, Q0S.459, P.O. Box 85500, 3508 GA, Utrecht, the Netherlands

    Cynthia Jongen & Freek Beekman

  2. Department of Nuclear Medicine, University of Amsterdam, Academic Medical Center, Amsterdam, the Netherlands

    Kora de Bruin & Jan Booij

  3. Department of Neuroscience & Pharmacology, University Medical Center Utrecht, Utrecht, the Netherlands

    Freek Beekman

  4. Department R3, Section Radiation, Detection & Matter, Technical University Delft, Delft, the Netherlands

    Freek Beekman

Authors
  1. Cynthia Jongen
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  2. Kora de Bruin
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  3. Freek Beekman
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  4. Jan Booij
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Corresponding author

Correspondence to Cynthia Jongen.

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Jongen, C., de Bruin, K., Beekman, F. et al. SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice. Eur J Nucl Med Mol Imaging 35, 1692–1698 (2008). https://doi.org/10.1007/s00259-008-0795-0

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  • DOI: https://doi.org/10.1007/s00259-008-0795-0

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