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Technetium Radiotracers for the Dopamine Transporter—RadioTracer, Inc., 73 Brookwood Road, Guilford, CT 06437-1804; 203-458-8437
Dr. Ronald M. Baldwin, Principal Investigator
Dr. Ronald M. Baldwin, Business Official
DOE Grant No. DE-FG02-98ER82653
Amount: $748,747
Changes in the brain’s dopamine transporter are involved in several important neurological and psychiatric disorders, such as Parkinson’s Disease and substance abuse. Radionuclide imaging of the dopamine transporter can measure neuronal loss non-invasively, as demonstrated by radiotracers labeled with the cyclotron-produced, radionuclide iodine-123, currently under commercial development. However, radiopharmaceuticals labeled with technitium-99m (Tc-99m) would be more practical for both clinical application and commercial development, because of the lower cost and readier availability of Tc-99m. This project will develop a Tc-99m labeled radiotracer for imaging the dopamine transporter with single-photon-emission computed tomography (SPECT). The working hypothesis is that conjugating a suitably substituted phenyltropane with a cyclopentadienyltricarbonyl metal complex would provide a tracer with high affinity and low, non-specific binding. The feasibility of this approach was shown in Phase I by first finding three compounds with good in-vitro affinity, demonstrating specific brain uptake in non-human primates by imaging, then labeling with technetium and rhenium. Phase II will develop mild, high-yield synthetic chemistry for making Tc-99m compounds, characterize the Tc-99m radiotracers carefully by in-vivo SPECT imaging in non-human primates and in-vitro pharmacology, and develop a "kit" type formulation as a production prototype for a radio-pharmaceutical drug product.
Commercial Applications and other Benefits as described by the awardee: The aging of the American population, along with the introduction of new drugs to both treat and slow Parkinson’s disease, should create a critical need for a sensitive accurate diagnostic test. The commercial availability of a Tc-99m SPECT agent for imaging of dopamine transporters should find wide application in diagnosing patients at risk for Parkinson’s, monitoring the progression of the disease, and advancing the development of effective preventive, palliative, and therapeutic treatments.