SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.
Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals.


METHODS
The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC.


RESULTS
The radioactivity curves measured as a function of time were reproducible and consistent with previous studies using PET imaging (ratio of striatum to cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant displacement of (11)C-raclopride by its stable analog. Finally, the device proved its capacity to accurately detect changes in (11)C-raclopride binding after a sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine levels.


CONCLUSIONS
These results show that the new device can monitor binding of PET ligands in anesthetized rodents in vivo, with high temporal resolution.
Zimmer
Luc
L
Centre d'Exploration et de Recherche Médicales par Emission de Positons, Biomedical Cyclotron, Lyon, France. zimmer@cermep.fr
Hassoun
Waddad
W
Pain
Frederic
F
Bonnefoi
Frederic
F
Lanièce
Philippe
P
Mastrippolito
Roland
R
Pinot
Laurent
L
Pujol
Jean-François
JF
Leviel
Vincent
V
D000818:Animals; D001610:Beta Particles; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists; D008024:Ligands; D008297:Male; D020891:Raclopride; D011869:Radioligand Assay; D011874:Radiometry / Q000295:instrumentation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D020891:Raclopride