The goal of this laboratory is to develop, evaluate, and implement new probes to examine the chemistry of the living brain with positron emission tomography (PET). With this technique, miniscule doses of a radioactively labeled drug are administered to a subject. The drug travels to the brain and binds to specific target sites, called receptors. The distribution and density of these targets in the brain can be measured with a PET camera. An example of this type of work is the measurement of the """"""""dopamine transporter,"""""""" which is the target site for the action of cocaine. The dopamine transporter is located on dopamine-containing neurons in the brain, and the degeneration of these specific neurons causes the symptoms of Parkinson's disease. Thus, a loss of these target sites can be used to aid in the diagnosis of Parkinson's disease. Although some of the PET radiolabeled drugs might be used for diagnostic purposes, the major use of these agents is to study the pathophysiology of disease. For example, we have implemented a PET probe for the serotonin transporter, which is the target site of antidepressant agents like Prozac. It is unlikely that the levels of the serotonin transporter would aid in diagnosis, but it may well be useful to assess its role in treatment or disease progression. Examples of our findings include: 1) We have found widespread loss of nicotine receptors in the brains of patients with Parkinson's disease. 2) We've studied a promising probe to measure inflammation. 3) We studied a cAMP enzyme involved in intracellular signaling. 4) Contrary to prior studies, we found that patients with alcoholism do not have a deficiency of serotonin transporters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002852-02
Application #
7312924
Study Section
(DIRP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lohith, Talakad G; Zoghbi, Sami S; Morse, Cheryl L et al. (2014) Retest imaging of [11C]NOP-1A binding to nociceptin/orphanin FQ peptide (NOP) receptors in the brain of healthy humans. Neuroimage 87:89-95
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Kimura, Yasuyuki; Siméon, Fabrice G; Zoghbi, Sami S et al. (2012) Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using 18F-SP203. Neuroimage 59:2124-30
Hirvonen, Jussi; Kreisl, William C; Fujita, Masahiro et al. (2012) Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy. J Nucl Med 53:234-40
Kannan, Pavitra; Brimacombe, Kyle R; Kreisl, William C et al. (2011) Lysosomal trapping of a radiolabeled substrate of P-glycoprotein as a mechanism for signal amplification in PET. Proc Natl Acad Sci U S A 108:2593-8
Kannan, Pavitra; Telu, Sanjay; Shukla, Suneet et al. (2011) The ""specific"" P-glycoprotein inhibitor Tariquidar is also a substrate and an inhibitor for breast cancer resistance protein (BCRP/ABCG2). ACS Chem Neurosci 2:82-9
Kimura, Yasuyuki; Siméon, Fabrice G; Hatazawa, Jun et al. (2010) Biodistribution and radiation dosimetry of a positron emission tomographic ligand, 18F-SP203, to image metabotropic glutamate subtype 5 receptors in humans. Eur J Nucl Med Mol Imaging 37:1943-9
Kannan, Pavitra; Brimacombe, Kyle R; Zoghbi, Sami S et al. (2010) N-desmethyl-loperamide is selective for P-glycoprotein among three ATP-binding cassette transporters at the blood-brain barrier. Drug Metab Dispos 38:917-22

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