PET AND SPECT IMAGING OF THE DOPAMINERGIC SYSTEM

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Positron emission tomography (PET) or single photon emission computed tomography (SPECT) have been used as unique non-invasive tools for the development of quantitative tracer kinetic studies for the measurement of the anatomic distribution and rates of specific biochemical processes on dopaminergic neurotransmission. The utility of these techniques in basic and clinical research in these areas has prompted us to continue exploring new agents for PET and SPECT studies. Further development of these techniques depends upon the availability of more potent and selective agents labeled with isotopes suitable for use with varied imaging instrumentation. In Phase I, the feasibility of synthesizing PET and SPECT agents suitable for imaging the Dopamine transporter was demonstrated. Preliminary PET and SPECT studies were conducted and parameters were identified which need to be optimized in order to commercialize the products. Proposed studies seek to continue the development of promising ligands with therapeutic PET and SPECT imaging potential for such neurological disorders as Parkinson's Disease. Approaches continue those proved successful in our Phase I program, and will include the Imaging of the Dopamine Transporter (DAT) with [123I]beta-CIT; the preparation of a "kit" for the rapid synthesis of [125I]- and [123I]beta-CIT; the synthesis of (1S)-(+)-beta-CIT (Inactive Isomer) for the assessment of non-specific uptake; the further development of selective probes for the DAT and the synthesis of N-Fluoroalkyl analogs of beta-CIT which can be labeled with 18F for PET imaging or 123I for SPECT imaging.