Nuclear Medicine and Biology
Volume 36, Issue 7 , Pages 721-727, October 2009

Improved work-up procedure for the production of [18F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke☆

This work is dedicated to the memory of Prof. George Just.

  • Gassan Massaweh

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Esther Schirrmacher

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Christian la Fougere

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • Department of Nuclear Medicine, Ludwig-Maximilians University, Munich, Germany
    • ,
  • Miriam Kovacevic

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Carmen Wängler

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Dean Jolly

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Paul Gravel

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Andrew J. Reader

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • ,
  • Alexander Thiel

      Affiliations

    • Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
    • Corresponding Author InformationCorresponding authors. Ralf Schirrmacher is to be contacted at Tel.: +1 514 398 1624; fax: +1 514 398 8195. Alexander Thiel, Department of Neurology and Neurosurgery, McGill University at Lady Davis Institute for Medical Research, Montreal, Quebec, Canada. Tel.: +1 514 340 8222 2094; fax: +1 514 340 7567.
    • ,
  • Ralf Schirrmacher

      Affiliations

    • McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    • Corresponding Author InformationCorresponding authors. Ralf Schirrmacher is to be contacted at Tel.: +1 514 398 1624; fax: +1 514 398 8195. Alexander Thiel, Department of Neurology and Neurosurgery, McGill University at Lady Davis Institute for Medical Research, Montreal, Quebec, Canada. Tel.: +1 514 340 8222 2094; fax: +1 514 340 7567.

Received 24 February 2009; received in revised form 19 May 2009; accepted 27 May 2009. published online 30 July 2009.

Abstract 

Introduction

The central benzodiazepine receptor (cBZR)–gamma-aminobutyric acid (GABAA) receptor complex in the human brain plays an important role in many neurological and psychiatric disorders. 18F-Labeled flumazenil ([18F]FZ) provides a potentially useful tracer to investigate those disorders by means of positron emission tomography (PET).

Methods

[18F]Flumazenil was synthesized from its nitro-precursor Ro 15-2344 in DMF at high temperatures between 150°C and 160°C. Other solvents like acetonitrile and dimethylsulfoxide were also investigated as reaction media. A new HPLC method for the final purification of [18F]FZ was developed to circumvent some difficulties associated with a previously published procedure sometimes led to a contamination of [18F]FZ with Ro 15-2344. The final purification of the radiotracer was achieved using a Waters Symmetry Prep C18 HPLC column with elution with 0.05 M sodium acetate (NaOAc) buffer (pH 5)/THF/MeOH (80:10:10).

Results

[18F]FZ could be synthesized in reproducible radiochemical yields (RCYs) of 15–20% (decay corrected to EOB) after 80 min overall synthesis time. The synthesized [18F]FZ was applied for the first time in a human PET study in a patient with ischemic right middle cerebral artery stroke using the HRRT high-resolution research scanner (Siemens Medical Solution, Knoxville, TN, USA).

Conclusions

[18F]FZ is a potentially useful GABA receptor-binding PET ligand. A modified procedure for its preparation in reproducibly high radiochemical yields has been described and the [18F]FZ thus produced has been used successfully in a pilot clinical study.

Keywords: Central benzodiazepine receptor, Flumazenil, HRRT scanner, Stroke, PET imaging

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☆ This work was supported in part by a research grant from the Natural Sciences and Engineering Council Canada (NCERC) to R. Schirrmacher and a Canadian Institutes of Health Research (CIHR) grant (Nr. MOP8444) to A. Thiel.

PII: S0969-8051(09)00149-8

doi:10.1016/j.nucmedbio.2009.05.008

Nuclear Medicine and Biology
Volume 36, Issue 7 , Pages 721-727, October 2009

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