Production of fluorine-18 labeled (3-N-methyl)benperidol for PET investigation of cerebral dopaminergic receptor binding.

The multi-millicurie synthesis of the D-2 receptor ligand [18F](3-N-methyl)benperidol (NMB; 1-[3-(4'- [18F]fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1- benzimidazolinyl)piperidine) is described. [18F]NMB was produced via a 3-step reaction sequence with an overall radiochemical yield of 5-10% and a specific activity greater than 3000 Ci/mmol within 100 min. In vitro binding assays indicated that NMB has high affinity for D-2 receptors in primate brain (K1 = 3.6 nM), with a receptor specificity exceeding that of spiperone. The technique described here permits the routine production of 10-20 mCi of this promising radiopharmaceutical for PET study of D-2 receptor binding in vivo.

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.