Sigma receptors are non-opioid, non-dopaminergic binding sites which have been implicated in psychoses, neurodegeneration, and the physiological aspects of motor disorders such as tardive dyskinesia and dystonia. Sigma receptors are observed to be most abundant in the cerebellum, hippocampus, cranial nerve nuclei, and red nucleus. The motor side effects of haloperidol and related neuroleptics, which bind with high affinity, may be mediated by sigma receptors. N1-3-Fluoropropyl-N4-2-([3,4-dichlorophenyl]lethyl)piperazine (BD 1304) is a high affinity and specific ligand for the sigma receptor. BD 1304 exhibits high affinity (Ki 0.39 nM. [3H]pentazocine) for the sigma receptor, but displays Ki values greater than 10,000 nM for PCP. D2- dopamine, kappa-opiate, and muscarinic binding sites. As an indication of the binding potential of this ligand, the Purkinje layer of the cerebellum exhibits [3H] pentazocine binding to the extent of 515 fmol/mg tissue while the binding in the frontal cortex is 152 fmol/mg tissue. We have prepared fluorine-18 labeled BD 1304 in 49 plus/minus 9% radiochemical yield (corrected for decay) following HPLC purification. The synthesis is composed of three major stages. Stage 1 is the separation of [18F] from the [180]H20 via simple ion exchange resin which is completed within 20-30 minutes of EOB. Stage 2 is the reaction and purification of the product which requires approximately 60 min. The third stage is the formulation. The HPLC purification provided a product with radiochemical (>99%) purity. The specific activity for the product, determined in two separate preparations was 4.0 and 3.7 Ci/mumol (EOB). Thus, starting from 5.8 mCi of [18F]fluoride. 1.8 mCi {31%; (45% corrected)} of product was collected from the HPLC column in approximately 60 min.
