Alterations in the CNS noradrenergic system are important in the pathophysiology of depression, anxiety disorders and drug addiction. A positron emission tomography (PET) imaging agent for the norepinephrine transporter (NET) would provide a powerful tool for the study of the noradrenergic system in living humans and non-human primates. Such an imaging agent could be used to determine regional brain NET density distribution in psychiatric illnesses before and after treatment was well as to determine the in vivo pharmokinetic and pharmacodynamic properties of drugs with affinity for the NET. This proposal outlines four specific aims for developing a NET imaging agent. First candidate molecules will be synthesize and characterized in vitro for their affinity and selectivity for the NET. Second, radiolabeling methods will be developed to produce radioligands suitable for PET imaging studies. Third, radioligands will be evaluated for their imaging characteristics through autoradiography on brain slices and biodistrubution in rats. Finally, promising candidates will be used for PET studies in non-human primates for NET density quantitation and dose-occupancy studies with reboxetine, a new NET-selective antidepressant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30MH013017-01
Application #
6310900
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (02))
Program Officer
Goldschmidts, Walter L
Project Start
2001-03-01
Project End
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$20,662
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322