In vivo labeling of the dopamine D2 receptor with N-¹¹C-methyl-benperidol

A new dopamine D2 receptor radiotracer, N-¹¹C-methyl-benperidol (¹¹C-NMB), was prepared and its in vivo biologic behavior in mice and a baboon was studied. Carbon-11-NMB was determined to bind to specific sites characterized as dopamine D2 receptors. The binding was saturable, reversible, and stereospecific. Kinetic studies in the dopamine D2 receptor-rich striatum showed that ¹¹C-NMB was retained five times longer than in receptor-devoid regions, resulting in a high maximum striatal-to-cerebellar ratio of 11:1 at 60 min after injection. From frontal cortex and cortex, on the other hand, the tracer washed out as rapidly as it did from cerebellum, resulting in tissue-to-cerebellar ratios close to one in these regions at any time after injection. Blocking studies confirmed the specificity and selectivity of the ¹¹C-NMB binding to the dopamine D2 receptor. A PET study with ¹¹C-NMB of the baboon brain revealed highly selective labeling of dopamine D2 receptor sites which was blocked by preinjection of raclopride.