Cerebral kinetics of the dopamine D(2) receptor ligand [(123)I]IBZM in mice.
BACKGROUND
In vivo small animal imaging of the dopaminergic system is of great interest for basic and applied neurosciences, especially in transgenic mice. Small animal SPECT is particularly attractive because of its superior spatial resolution and tracer availability. We investigated the kinetics of the commercial dopamine D(2) receptor (DZR) ligand [(123)I]IBZM in mice as a prerequisite for an appropriate design of translational SPECT imaging between mice and humans.


METHODS
Cerebral kinetics of [(123)I]IBZM under isoflurane anaesthesia were assessed by autoradiography in mice sacrificed at 30, 60, 120 and 200 min after iv injection. To explore the possible effects of isoflurane anaesthesia, an additional mice group was only anaesthetized for 20 min before being sacrificed at 140 min (putative time of single-scan SPECT analysis).


RESULTS
Maximum [(123)I]IBZM uptake in the striatum (D(2)R-rich; 10.5+/-2.7 %ID/g) and cerebellum (D(2)R-devoid; 2.4+/-0.7 %ID/g) was observed at 30 min after injection. Thereafter, [(123)I]IBZM uptake decreased slowly in striatum and rapidly in the cerebellum (200 min: 5.3+/-1.9 and 0.4+/-0.2 %ID/g, respectively). The striatum-to-cerebellum (S/C) [(123)I]IBZM uptake ratio increased from 4.6+/-1.2 at 30 min to 11.6+/-2.6 at 120 min. The S/C ratio at 200 min was highly variable (17.8+/-10.1), possibly indicating pseudo-equilibration in some animals. In mice, which were only anaesthetized between 120 and 140 min, a higher S/C ratio of 17.0+/-5.1 was observed.


CONCLUSIONS
The present study suggests that [(123)I]IBZM is a suitable ligand for D(2)R-SPECT in mice. Although a single-scan analysis may be a pragmatic semi-quantitative approach, tracer kinetic analyses on dynamic SPECT data should be pursued. The interfering effects of isoflurane anaesthesia need to be considered.
Meyer
Philipp T
PT
Department of Neurology, University Hospital Aachen, 52074 Aachen, Germany. pmeyer@ukaachen.de
Salber
Dagmar
D
Schiefer
Johannes
J
Cremer
Markus
M
Schaefer
Wolfgang M
WM
Kosinski
Christoph M
CM
Langen
Karl-Josef
KJ
D000758:Anesthesia / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging*; D007530:Isoflurane / Q000009:adverse effects; D007700:Kinetics; D051379:Mice; D023421:Models, Animal; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000032:analysis*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D018685:Anesthetics, Inhalation; D001549:Benzamides; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D007530:Isoflurane