Technetium Radiotracers for the Dopamine Transporter

50311-98-I 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: $74,973 Changes in the dopamine transporter are involved in important neurological and psychiatric disorders, including Parkinson¿s Disease and substance abuse. Radionuclide imaging of the dopamine transporter can measure neuronal loss noninvasively, as demonstrated by radiotracers labeled with the cyclotron-produced radionuclide iodine-123. Radiopharmaceuticals labeled with technetium-99m (Tc-99m) would be more practical for clinical application and commercial development because of the lower cost and readier availability of Tc-99m. The goal of this project is to develop a Tc-99m-labeled radiotracer for imaging the dopamine transporter with single photon emission computed tomography (SPECT). The working hypothesis is that attaching a suitable substituted phenyltropane with an indenyl- or cyclopentadienyltricarbonyl metal complex will give a tracer with a high affinity and low nonspecific binding. This project will test proof of principle by synthesizing representative rhenium complexes and measuring in vitro binding and lipophilicity. Candidates with the highest affinity will be labeled with Tc-99m and the specific dopamine transporter binding of the radiolabeled complex will be measured. Phase II studies will follow up with in vivo binding by SPECT imaging of the Tc-99m complexes, developing labeling methods for a ¿kit¿ product, and extending the structure-activity relationships. Commercial Applications and Other Benefits as described by the awardee: The commercial availability of a Tc-99m SPECT agent for imaging of dopamine transporters will find wide application in Parkinson¿s disease to diagnose patients at risk, to monitor progression of the disease, and to advance the development of effective preventive, palliative, and therapeutic treatments._