The purpose of this project was to synthesize Raclopride labeled with carbon-Il (T1/2 = 20.4 min), a cyclotron produced, positron-emitting radionuclide, which will permit imaging the brain utilizing positron emission tomography (PET). Drs. Alan Breier and Andrea de Bartolomes are interested in using PET and [11C]Raclopride to study the displacement of [11C]Raclopride in schizophrenia patients and healthy controls. The purpose of the study is to examine dopamine function using displacement of [11C]Raclopride by methylphenidate induced increases in synaptic dopamine.
The specific aims are to develop a method for determining estimates of in vivo synaptic dopamine concentrations in humans, and to utilize this method to test the hypothesis that schizophrenia is associated with increased methylphenidate-induced dopamine release. A bisphenol precursor of Raclopride was reacted with [11C]CH3I to produce [11C]Raclopride. Using an adaptation of methods described in the literature, [11C]CH3I was trapped in a solution of the bisphenol precursor (2 mg), 500 microL DMSO, and 5 microL of 5N NaOH in a sealed vessel at ambient temperature. The vessel was then heated at 80 for 3 min. The solution was diluted with 500 microL of HPLC solvent and injected onto a reversed phase column. The product was collected in a rotary evaporator. After evaporation of solvent and formulation, the product was sterilized by filtration through a 0.22 micro Millipore filter. A 20 microA/20min irradiation routinely produced about 25 mCi of product at end of synthesis (EOS) with a specific activity of approximately 400 mCi/umol (EOS). The yield was found to vary significantly with the amount of 5N NaOH that was used, and with the extent of the greenish color of the solution. Highest yields were obtained when 5 microL of 5N NaOH were used, the solution was light green in color, and the [11C]CH3I was trapped within about 5 min after adding the 5N NaOH. To date, six monkey studies have been performed. Satisfactory images have been obtained.
