A within-subject comparison of 6-[18F]fluoro-m-tyrosine and 6-[18F]fluoro-L-dopa in Parkinson's disease§

Authors

  • Catherine L. Gallagher MD,

    Corresponding author
    1. William S. Middleton Veterans Hospital, Madison, Wisconsin, USA
    2. Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    • University of Wisconsin Department of Neurology, 2500 Overlook Terrace Dr., Madison, WI, 53705, USA
    Search for more papers by this author
  • Bradley T. Christian PhD,

    1. University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA
    2. Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA
    Search for more papers by this author
  • James E. Holden PhD,

    1. University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA
    Search for more papers by this author
  • Onofre T. Dejesus PhD,

    1. University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA
    Search for more papers by this author
  • Robert J. Nickles PhD,

    1. University of Wisconsin, Department of Medical Physics, Madison, Wisconsin, USA
    Search for more papers by this author
  • Laura Buyan-Dent MD, PhD,

    1. Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    Search for more papers by this author
  • Barbara B. Bendlin PhD,

    1. William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA
    2. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    Search for more papers by this author
  • Sandra J. Harding MS,

    1. William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA
    2. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    Search for more papers by this author
  • Charles K. Stone MD,

    1. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    Search for more papers by this author
  • Barb Mueller BS,

    1. Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin, USA
    Search for more papers by this author
  • Sterling C. Johnson PhD

    1. William S. Middleton Veterans Hospital G.R.E.C.C., Madison, Wisconsin, USA
    2. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    Search for more papers by this author

  • Funding agencies: This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service and University of Wisconsin Institute for Clinical and Translational Research, funded through a National Institutes of Health Clinical and Translational Science Award (grant number 1UL1RR025011). This work was supported with the use of facilities at the William S. Middleton Memorial Veterans Hospital Geriatric Research Education and Clinical Center and the Waisman Laboratory for Brain Imaging and Behavior, Madison, Wisconsin.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Progression of Parkinson's disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[18F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[18F]fluoro-L-dopa. The objective of this study was to evaluate 6-[18F]fluoro-m-tyrosine relative to 6-[18F]fluoro-L-dopa with partial catechol-O-methyltransferase inhibition as a biomarker for clinical status in Parkinson's disease. Twelve patients with early-stage Parkinson's disease, off medication, underwent Unified Parkinson Disease Rating Scale scoring, brain magnetic resonance imaging, and 3-dimensional dynamic positron emission tomography using equivalent doses of 6-[18F]fluoro-m-tyrosine and 6-[18F]fluoro-L-dopa with tolcapone, a catechol-O-methyltransferase inhibitor. Images were realigned within subject, after which the tissue-derived uptake rate constant was generated for volumes of interest encompassing the caudate nucleus, putamen, and subregions of the putamen. We computed both bivariate (Pearson) and partial (covariate of age) correlations between clinical subscores and tissue-derived uptake rate constant. Tissue-derived uptake rate constant values were correlated between the radiopharmaceuticals (r = 0.8). Motor subscores were inversely correlated with the contralateral putamen 6-[18F]fluoro-m-tyrosine tissue-derived uptake rate constant (|r| > 0.72, P < .005) but not significantly with the 6-[18F]fluoro-L-dopa tissue-derived uptake rate constant. The uptake rate constants for both radiopharmaceuticals were also inversely correlated with activities of daily living subscores, but the magnitude of correlation coefficients was greater for 6-[18F]fluoro-m-tyrosine. In this design, 6-[18F]fluoro-m-tyrosine uptake better reflected clinical status than did 6-[18F]fluoro-L-dopa uptake. We attribute this finding to 6-[18F]fluoro-m-tyrosine's higher affinity for the target, L-aromatic amino acid decarboxylase, and the absence of other major determinants of the uptake rate constant. These results also imply that L-aromatic amino acid decarboxylase activity is a major determinant of clinical status. © 2011 Movement Disorder Society

Ancillary