[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine--an in vivo imaging study with a dedicated small animal SPECT.

Abstract

This study assessed [123I]iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. Subsequent to baseline quantifications of D2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D2 receptors and dopamine transporters, respectively. Striatal baseline equilibrium ratios (V3'') of [123I]iodobenzamide binding were 1.42+/-0.31 (mean+/-SD). After pre-treatment with haloperidol and methylphenidate, V3'' values decreased to 0.54+/-0.46 (p<0.0001) and 0.98+/-0.48 (p=0.009), respectively. The decrease in [123I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [123I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [123I]iodobenzamide binding to D2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine.