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Yu-Shin Ding, PhDProfessor of Diagnostic Radiology Specialty: Yale PET Center Curriculum Vitae (pdf; 179KB)
Research Interests: My research concentrates primarily on the development of new methodologies to synthesize short half-lived radiopharmaceuticals and applying them towards investigation of biochemical transformations and drug mechanisms in primates and humans. My research has focused on the investigation of the functional significance of various neurotransmitter systems, such as dopamine, norepinephrine, serotonin, acetylcholine, as well as oncology and cardiology studies. I and my co-workers have previously developed many unique radiotracers, many involving multi-step sequences; for example, the F-18 (t1/2: 110 min) labeled catecholamines. We devised and carried out the first synthesis of no-carrier-added (NCA) F-18 labeled electron-rich aromatic rings and applied this strategy to the synthesis of NCA F-18 labeled catecholamines, which enabled the first PET studies to be carried out without producing vascular effects. We also employed the deuterium isotope effect in mechanistic studies to understand the behavior of F-18 labeled catecholamines in living systems. The research on catechol-O-methyltransferase (COMT) proposed in my FIRST award and DOD breast cancer grant provides links between basic neuroscience and drug research, drug development and oncology. Our recent data that showed relatively higher COMT activities in tumor tissue as compared to normal tissue from breast cancer patients support the promise of future PET investigation of this disease. We have successfully translated several radiotracers from pre-clinical studies in animals to clinical investigations in humans; for example, we developed C-11 labeled methylphenidate (Ritalin, a drug for the treatment of ADHD) and its active enantiomer, [11C]d-threo-methylphenidate, as ligands (t1/2 of 11C: 20 min) for the dopamine transporter. This development work allows the first studies of this drug in the human brain leading to a better understanding of the reinforcing abilities of psychostimulant drugs, and also has initiated investigations in drug abuse, alcoholism, obesity, Parkinson’s disease and normal aging. Our recent development of potent and selective radioligands to carry out PET imaging studies of nicotinic acetylcholine receptor (nAChR) and norepinephrine transporter (NET) systems in humans should provide an opportunity to better understand their roles in various CNS disorders, such as substance abuse, depression, ADHD, Parkinson’s disease and Alzheimer’s disease. |
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