In vivo evaluation of [I-123]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno [3,4-c]pyridin-5-one: a presumed dopamine D-4 receptor ligand for SPECT studies

摘要

[I-123]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one ([I-123]-ITCP), a presumed radioligand for visualization of the dopamine D-4 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 D-4 ligand and later with a a receptor ligand. Both experiments showed no observable competition. In conclusion, our findings indicate that [I-123]-ITCP is neither a dopamine D-4 receptor ligand nor a sigma receptor ligand. The exact nature of [I-123]-ITCP binding it, the brain remains to be elucidated. (c) 2005 Elsevier Inc. All rights reserved.