PET imaging of dopamine D2 receptors with [18F]fluoroclebopride in monkeys: effects of isoflurane- and ketamine-induced anesthesia.
The purpose of the present study was to determine whether positron emission tomography (PET) studies in monkeys with the dopamine (DA) D2 receptor ligand [18F]fluoroclebopride (FCP) would be significantly influenced by anesthetic induction with isoflurane (approximately 5.0%) compared to induction with 10 mg/kg ketamine. Five experimentally-naive adult male cynomolgus monkeys (Macaca fascicularis) were trained to sit calmly in a primate restraint chair. Before the first PET scan, each monkey was anesthetized, by mask, with isoflurane. After complete sedation, the monkey was intubated and anesthesia was maintained throughout the PET study by isoflurane (approximately 1.5%). At least 1 month later, a second PET study was conducted in which anesthesia was induced with ketamine and maintained by isoflurane (approximately 1.5%). Irrespective of induction anesthetic, there was a high uptake of [18F]FCP and a linear rate of washout from the basal ganglia for all monkeys. There were also no differences in time to peak uptake (approximately 25 min), in clearance half-life (t1/2 = 140-164 min) or in D2 binding (distribution volume ratios of 2.48 vs. 2.50). These results indicate that induction anesthetic did not differentially affect D2 binding of [18F]FCP in monkeys. Furthermore, the low variability between studies indicates that [18F]FCP is an excellent ligand for longitudinal studies of D2 receptors in nonhuman primates.
Nader
M A
MA
Department of Physiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Grant
K A
KA
Gage
H D
HD
Ehrenkaufer
R L
RL
Kaplan
J R
JR
Mach
R H
RH
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004347:Drug Interactions; D005462:Fluorine Radioisotopes; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D000777:Anesthetics; D001549:Benzamides; D005462:Fluorine Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C083673:fluoroclebopride; D007649:Ketamine; D007530:Isoflurane