Abstract

Loss of 5-HT (5-hydroxytryptamine, serotonin) neurons in Parkinson's disease has been established with both direct and indirect measurements. Direct measurements are performed on postmortem material and include techniques of immunochemistry and autoradiography, measurements which can not be applied in living patients. Indirect evidence is provided by reduced concentrations of 5-HT and its metabolites in the cerebrospinal fluid. These measurements are performed in living patients, but they do not provide a direct, quantitative estimate of 5-HT neurons and axon terminals in different regions of the brain. Preliminary data indicate that it is feasible to image the 5-HT transporter in the human brain with PET and carbon-11 McN5652 and that 5-HT transporter loss can be detected in patients with Parkinson's disease using this method. The purpose of this project is to quantitatively measure 5-HT transporter loss and gain and understanding of its clinical significance in Parkinson's disease. The following specific hypotheses will be addressed: 1) Radioligand binding to the 5-HT transporter is significantly reduced in Parkinson's disease: 2) Severity of clinical manifestations of Parkinson's disease correlates with the quantitative data derived from PET measurements. The long term goal of this project is to further elucidate the role of 5-HT neuronal loss in Parkinson's disease. This should lead to a better understanding of the role of serotonin enhancing drugs in treating patients with PD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014400-03
Application #
6124214
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Finkelstein, Judith A
Project Start
1997-12-01
Project End
2002-11-30
Budget Start
1999-12-15
Budget End
2002-11-30
Support Year
3
Fiscal Year
2000
Total Cost
$292,269
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Wang, Z Jane; Szabo, Zsolt; Lei, Peng et al. (2008) A Factor-Image Framework to Quantification of Brain Receptor Dynamic PET Studies. IEEE Trans Signal Process 53:3473-3487
Jane Wang, Z; Qiu, Peng; Ray Liu, K J et al. (2005) Model-Based Receptor Quantization Analysis for PET Parametric Imaging. Conf Proc IEEE Eng Med Biol Soc 6:5908-11
McCann, Una D; Szabo, Zsolt; Seckin, Esen et al. (2005) Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB. Neuropsychopharmacology 30:1741-50
Kerenyi, Levente; Ricaurte, George A; Schretlen, David J et al. (2003) Positron emission tomography of striatal serotonin transporters in Parkinson disease. Arch Neurol 60:1223-9
Szabo, Zsolt; McCann, Una D; Wilson, Alan A et al. (2002) Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med 43:678-92
Varga, Jozsef; Szabo, Zsolt (2002) Modified regression model for the Logan plot. J Cereb Blood Flow Metab 22:240-4
Wang, Y; Adali, T; Xuan, J et al. (2001) Magnetic resonance image analysis by information theoretic criteria and stochastic site models. IEEE Trans Inf Technol Biomed 5:150-8
Hilton, J; Yokoi, F; Dannals, R F et al. (2000) Column-switching HPLC for the analysis of plasma in PET imaging studies. Nucl Med Biol 27:627-30
Szabo, Z; Scheffel, U; Mathews, W B et al. (1999) Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand. J Cereb Blood Flow Metab 19:967-81
Wang, Yue; Adaly, Tulay; Kung, Sun-Yuan et al. (1998) Quantification and Segmentation of Brain Tissues from MR Images: A Probabilistic Neural Network Approach. IEEE Trans Image Process 7:1165-1181