Abstract
Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin2A receptor and the dopamine re-uptake site by use of [3H]-(S)-citalopram, [18F]altanserin and [125I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean ± SD) of [3H]-(S)-citalopram from 1.5±0.19 to 0.81±0.19 (P<0.05), whereas isoflurane and halothane increased the ratio from 1.5±0.19 to 1.9±0.24 and 2.1±0.13 (P<0.05), respectively. Only with the zoletile mixture did the ratio remain unaltered. None of the tested anaesthetics affected the target-to-background ratio of [18F]altanserin. The [125I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4±0.81 to 10.1±1.4, P<0.05) and isoflurane (from 12.4±0.81 to 9.5±1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated.
References
Elfving B, Bjørnholm B, Knudsen G. Predosing with the unlabeled "inactive" enantiomer as a tool for improvement of the PET signal. Synapse 2002; 46:125–127.
Tao R, Auerbach SB. Anesthetics block morphine-induced increases in serotonin release in rat CNS. Synapse 1994; 18:307–314.
Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N. Ketamine alters the availability of striatal dopamine transporter as measured by [11C]β-CFT and [11C]β-CIT-FE in the monkey brain. Synapse 2001; 42:273–280.
Minami K, Minami M, Harris RA. Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics. J Pharmacol Exp Ther 1997; 281:1136–1143.
Rao TS, Contreras PC, Cler JA, et al. Contrasting neurochemical interactions of tiletamine, a potent phencyclidine (PCP) receptor ligand, with the N-methyl-d-aspartate-coupled and -uncoupled PCP recognition sites. J Neurochem 1991; 56:890–897.
Martin DC, Adams RJ, Aronstam RS. The influence of isoflurane on the synaptic activity of 5-hydroxytryptamine. Neurochem Res 1990; 15:969–973.
Votaw JR, Byas-Smith M, Martarello L, Howell LL, Kilts CD, Wilcox K, Goodman MM. Interaction of isoflurane and sevoflurane with the dopamine transporter. J Nucl Med Suppl 2001; 42:213P.
Wollmer P, Moresco RM, Simonelli P, et al. Evaluation of [O-methyl-11C]fluvoxamine as a tracer for serotonin re-uptake sites. Nucl Med Biol 2000; 27:177–181.
Guilloteau D, Emond P, Baulieu JL, et al. . Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3 β -(4'-methylphenyl)nor-tropane (PE2I). Nucl Med Biol 1998; 25:331–337.
Poyot T, Conde F, Gregoire MC, et al. Anatomic and biochemical correlates of the dopamine transporter ligand [11C]PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-l-dopa. J Cereb Blood Flow Metab 2001; 21:782–792.
Acknowledgements
This work was supported by a research grant from The 1991 Pharmacy Foundation, Health Insurance Fund and the Lundbeck Foundation. We thank Denis Guilloteau, Service de Médecine Nucléaire, Tours, France for labelling [125I]PE2I. The excellent technical assistance by Inge Møller, Neurobiology Research Laboratory, University Hospital Rigshospitalet, Denmark is much appreciated.
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Elfving, B., Bjørnholm, B. & Knudsen, G.M. Interference of anaesthetics with radioligand binding in neuroreceptor studies. Eur J Nucl Med Mol Imaging 30, 912–915 (2003). https://doi.org/10.1007/s00259-003-1171-8
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DOI: https://doi.org/10.1007/s00259-003-1171-8