[123I]B-CIT SPECT Imaging of Striatal Dopamine Transporter in TS

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Malison, Robert, MD

Several lines of information suggest that a specific chemical messenger in the brain called dopamine is involved in the cause of Tourette Syndrome (TS). In TS patients, tics and other repetitive behaviors are made worse by medications (e.g., methylphenidate) which increase dopamine levels, while those that reduce dopamine (e.g., haloperidol and pimozide) reduce tics. In addition, studies of the fluid which bathes the brain have shown evidence of changes in dopamine metabolism in TS subjects.Among the many possible brain regions, many investigators believe that an area known as the basal ganglia is involved. That is because this part of the brain controls many normal movements and the fact that it is the target of many dopamine nerve cells. In a study of brains from deceased TS patients, researchers found evidence of increased numbers (35-50%) of a specific brain protein known as the dopamine transporter in the basal ganglia. This protein, which is located on the endings of nerve cells, plays a central role in the regulation of dopamine transmission and serves as a marker for a number of dopamine neurons. Thus, increases in dopa¬mine transporters may reflect a greater number of dopamine nerve cell endings in the basal ganglia of TS patients. We have developed a promising non-invasive tool for measuring levels of dopamine transporters in living subjects.A radioactive medication referred to as [123I]ß-CIT (2ß-carbomethoxy-3ß-(4-iodo¬phenyl) tropane) enables the levels of dopamine transporters to be quantified in the living human brain with a modern brain imaging technique known as SPECT (single photon emission computed tomography). We have recently published a pilot study using [123I]?-CIT to measure dopamine transporter levels directly in adult TS subjects (Malison et al., 1995). Our preliminary findings are consis¬tent with postmortem data and show a 38% elevation in striatal dopamine transporter levels in 5 TS subjects as compared to 5 age-and gender-matched healthy controls. The aim of the current study is to confirm these findings in a larger population of TS subjects, including individuals who also have co-occurring obsessions and/or compulsions. By understanding changes in dopamine chemistry in the brains of individuals with TS, we hope to improve our understanding of different subtypes of the disorder which will ultimately lead to better treatments and ultimately the prevention of the disorder. Robert T. Malison, M.D. Yale School of Medicine, New Haven, CT Award $25,000 Tourette Association of America Inc. – Research Grant Award 1996