title: In vivo evaluation of [(123)I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one: a presumed dopamine D4 receptor ligand for SPECT studies.
abstract: [(123)I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one ([(123)I]-ITCP), a presumed radioligand for visualization of the dopamine D4 receptor by single photon emission computed tomography, was evaluated in vivo in mice and rabbits. This new radioiodinated tracer exhibited high brain uptake (3.64% injected dose per gram of tissue at 10 min p.i.) in mice. No significant amounts (less than 5%) of labeled metabolites were present in the brain, as demonstrated by a metabolite study. Regional brain distribution in rabbits showed atypical CNS uptake with consistently low values in the cortex and high values in other brain parts including cerebellum. Saturable binding was confirmed by a competition experiment with unlabeled product. Selectivity was assessed by competition experiments with a known dopamine D4 ligand and later with a sigma receptor ligand. Both experiments showed no observable competition. In conclusion, our findings indicate that [(123)I]-ITCP is neither a dopamine D4 receptor ligand nor a sigma receptor ligand. The exact nature of [(123)I]-ITCP binding in the brain remains to be elucidated.
authors.affiliation: Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Gent University, B-9000 Gent, Belgium. ludovicus.staelens@ugent.be
authors.forename: Ludovicus
authors.initials: L
authors.lastname: Staelens
authors.forename: Ruth
authors.initials: R
authors.lastname: Oltenfreiter
authors.forename: Peter
authors.initials: P
authors.lastname: Blanckaert
authors.forename: Veerle
authors.initials: V
authors.lastname: Kersemans
authors.forename: Katia
authors.initials: K
authors.lastname: Vandenbulcke
authors.forename: Christophe
authors.initials: C
authors.lastname: Van De Wiele
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011728:Pyridones / Q000493:pharmacokinetics*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C504059:(123)I-ITCP; D001578:Benzopyrans; C493600:Drd4 protein, mouse; D011728:Pyridones; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4