A technique for standardized central analysis of 6-18F-fluoro-L- DOPA PET data from a multicenter study

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  • Alan L. Whone, Hammersmith Hospital
  • ,
  • Dale L. Bailey, Northern Sydney Cancer Centre, Royal North Shore Hospital
  • ,
  • Philippe Remy, Department of Integrated Structural Biology, IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale (INSERM) U964/Université de Strasbourg
  • ,
  • Nicola Pavese
  • David J. Brooks

We have recently completed a large 6-18F-fluoro-L-DOPA ( 18F-DOPA) PET study comparing rates of loss of dopamine terminal function in Parkinson's disease (PD) patients taking either the dopamine agonist ropinirole or L-DOPA. This trial involved a "distributed acquisition/centralized analysis" method, in which 18F-DOPA images were acquired at 6 different PET centers around the world and then analyzed at a single site. To our knowledge, this is the first time such a centralized approach has been employed with 18F-DOPA PET and this descriptive basic science article outlines the methods used. Methods: One hundred eighty-six PD patients were randomized (1:1) to ropinirole or L-DOPA therapy, and 18F-DOPA PET was performed at baseline and again at 2 y. The primary outcome measure was the percentage change in putamen 18F-DOPA influx rate constant (Ki) from Patlak graphical analysis. Dynamic images were acquired and reconstructed using each center's individual protocols before being transferred to the site performing the central analysis. Once there, individual parametric Ki images were created using a single analysis program without file formats being transformed from the original. Parametric images were then normalized to standard space and K i values extracted with a region of interest analysis. Significant Ki changes were also localized at a voxel level with statistical parametric mapping. These processes required numerous checks to ensure the integrity of each dataset. Results: Three hundred twenty-five (170 baseline, 155 follow-up) dynamic PET datasets were acquired, of which 12 were considered uninterpretable due to missing time frames, radiopharmaceutical problems, lack of measured attenuation correction, or excessive head movement. In those datasets suitable for central analysis, after quality control and spatial normalization of the images had been applied, putamen 18F-DOPA signal decline was found to be significantly (one third) slower in the ropinirole group compared with that of the L-DOPA group. Conclusion: Paired 18F-DOPA-PET images acquired from multiple sites can be successfully analyzed centrally to assess the efficacy of potential disease-modifying therapies in PD. However, numerous options must be considered and data checks put in place before adopting such an approach. Centralized analysis offers the potential for improved detection of outcomes due to the standardization of the analytic approach and allows the analysis of large numbers of PET studies.

Original languageEnglish
JournalJournal of Nuclear Medicine
Pages (from-to)1135-1145
Number of pages11
Publication statusPublished - 1 Jul 2004
Externally publishedYes

    Research areas

  • F-DOPA, Central analysis, Parkinson's disease, PET, Progression

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