SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice.
OBJECTIVE
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.
Jongen
Cynthia
C
Image Sciences Institute, University Medical Center Utrecht, , Utrecht, the Netherlands. c.jongen@umcutrecht.nl
de Bruin
Kora
K
Beekman
Freek
F
Booij
Jan
J
D000438:Alcohols / Q000633:toxicity; D000661:Amphetamine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007462:Iodobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
D000438:Alcohols; D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; C426805:idobenzamide; D000661:Amphetamine; D004298:Dopamine