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Author Notes:

Correspondence: Yoland Smith, PhD., Yerkes National Primate Research Center Emory University 954 Gatewood Rd NE Atlanta, GA 30329; Email: ysmit01@emory.edu; Tel: (404) 727 7519

Acknowledgments: Thanks are due to Susan Jenkins for technical assistance and Jim Bogenpohl, Xing Hu and Adriana Galvan for training with monkey behavior.

The authors are also grateful to Professor Carlos Avendano from the University Autonoma in Madrid who has helped with the design and interpretation of stereological data.

Subjects:

Research Funding:

This work was supported by a grant from the National Parkinson Foundation and the Yerkes Primate Center NIH/NCRR base grant (RR00165).

Keywords:

  • Parkinson’s disease
  • brain imaging
  • transporter
  • dopamine
  • striatum
  • MPTP
  • monkey
  • primate
  • substantia nigra
  • midbrain
  • animal model

18F-FECNT: Validation as PET Dopamine Transporter Ligand in Parkinsonism

Journal Title:

Experimental Neurology

Volume:

Volume 226, Number 2

Publisher:

, Pages 265-273

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The positron emission tomography (PET) tracer 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane (18F-FECNT) is a highly specific ligand for dopamine transporter (DAT) that yields higher peak striatum-to-cerebellum ratios and offers more favorable kinetics than most 18F-radiolabeled DAT ligands currently available. The goal of this study is to validate the use of 18F-FECNT as a PET radiotracer to assess the degree of striatal dopamine terminals denervation and midbrain dopaminergic cell loss in MPTP-treated parkinsonian monkeys. Three rhesus monkeys received weekly injections of MPTP (0.2-0.5 mg/kg) for 21 weeks, which resulted in the progressive development of a moderate level of parkinsonism. We carried out 18F-FECNT PET at baseline (twice; ten weeks apart) and at week 21 post-MPTP injections. Postmortem stereological cell counts of dopaminergic neurons in the ventral midbrain, and intensity measurements of DAT and tyrosine hydroxylase (TH) immunoreactivity in the striatum were performed and correlated with striatal and ventral midbrain PET data. Three additional monkeys were used as controls for midbrain dopaminergic cell counts, and striatal DAT or TH immunoreactivity measurements. The correlation and coefficient of variance between 18F-FECNT test-retest specific uptake ratios were 0.99 (R2) and 2.65%, respectively. The 18F-FECNT binding potential of the ventral midbrain and striatal regions was tightly correlated with postmortem stereological cell counts of nigral dopaminergic neurons (R2 = 0.91), and striatal DAT (R2 = 0.83) or TH (R2 = 0.88) immunoreactivity intensity measurements. These findings demonstrate that 18F-FECNT is a highly sensitive PET imaging ligand to quantify both striatal dopamine denervation and midbrain dopaminergic cell loss associated with parkinsonism.

Copyright information:

© 2010 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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