A comparative PET-study of five carbon-11 or fluorine-18 labelled salicylamides. Preparation and in vitro dopamine D-2 receptor binding.

Five 11C- or 18F-labelled salicylamides ([11C]raclopride (I), [11C]eticlopride (II), [18F]NCQ 258 (III), [18F]NCQ 134 (IV) and [18F]NCQ 135 (V] were prepared. The total radiochemical yields of I-V from EOB were 3-30% (decay-corrected) with an overall synthesis time of 40-110 min. All compounds were isolated by semi-preparative HPLC and the radiochemical purity was greater than 99%. I-V were in separate experiments injected into Cynomolgus monkeys for PET-examination of ligand distribution in brain in vivo. I-V passed rapidly across the blood-brain barrier. With both analogs I and II there was a high uptake in the striatum, a region with a high density of dopamine D-2 receptors. With the 18F-labelled analogs III and IV, the uptake in the striatum was almost identical to that in the dopamine receptor poor cerebellum whereas the striatal uptake of V was clearly higher than in the cerebellum. Unlabelled I-V (raclopride, eticlopride, NCQ 258 (VII), NCQ 134 (VIII) and NCQ 135 (IX)) were also prepared and examined in vitro using [3H]raclopride and [3H]spiperone binding to rat striatal dopamine D-2 receptors. A significantly lower affinity was shown for NCQ 258 and NCQ 134 (5 times) compared to that of raclopride and eticlopride, respectively, whereas the affinity of NCQ 135 was similar to that of eticlopride.