Predosing with the unlabeled "inactive" enantiomer as a tool for improvement of the PET signal.
In this study we investigated whether the PET signal of labeled (S)-citalopram could be improved by predosing with the unlabeled distomer (R)-citalopram. Ten minutes before intravenous injection of 1.5 MBq [(3)H]-(S)-citalopram, rats were given i.v. 0.9% saline, 16 or 24 microg (R)-citalopram. Sixty minutes after injection of [(3)H]-(S)-citalopram, the brains were dissected into eight regions. The binding obtained in each brain region was compared to cerebellum as a reference region. Predosing with saline, 16 and 24 microg (R)-citalopram yielded thalamus/cerebellum ratios of 1.6 +/- 0.12, 1.6 +/- 0.12, and 1.1 +/- 0.26 (means +/- SD), respectively. It is concluded that the nonspecific binding of radiolabeled (S)-citalopram cannot be reduced by predosing with the 150 times less active enantiomer (R)-citalopram, possibly due to the pool of nonspecific sites being too large for blocking.
Elfving
Betina
B
Neurobiology Research Unit N9201, University Hospital Rigshospitalet, DK-2500 Copenhagen, Denmark. belfving@pet.rh.dk
Bjørnholm
Berith
B
Knudsen
Gitte M
GM
D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000378:metabolism; D015283:Citalopram / Q000493:pharmacokinetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed / Q000379:methods
D002352:Carrier Proteins; D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat