A TC-99M SPECT IMAGING AGENT WHICH TARGETS THE DOPAMINE TRANSPORTER IN PRIMATE BRAIN

The dopamine transporter (DAT), located presynaptically on dopamine ne urons, provides a marker for certain neurological diseases. In particu lar, the DAT is depleted in Parkinson's disease, and the extent of dep letion correlates with the loss of dopamine. Herein we describe the de sign, synthesis, and biological evaluation of technepine, the first Tc -99m-labeled SPECT imaging agent which targets the dopamine transporte r in striatum. We have demonstrated that the DAT can accommodate a che lating unit attached to the 8-amine function of a tropane skeleton. Fu rther, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide Tc-99m across the blood-brain barri er in sufficient quantity to obtain in. vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new rece ptor and transporter-mediated Tc-99m agents which can label specific t ransporter and receptor targets in the central nervous system.