In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat

Stefanie Dedeurwaerdere, Marie Claude Gregoire, Lucy Vivash, Peter Roselt, David Binns, Christopher Fookes, Ivan Greguric, Tien Pham, Christian Loc'H, Andrew Katsifis, Rodney J. Hicks, Terence J. O'Brien, Damian E. Myers

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20 Citations (Scopus)


Purpose: [11C]Flumazenil shows promise as a clinical and research PET radiotracer to image changes in GABAA central benzodiazepine receptor (cBZR), but its widespread use has been limited by practical limitations of [11C]. This study evaluated the imaging characteristics of two fluorinated PET radiotracers in rats in vivo: [ 18F]fluoroflumazenil ([18F]FFMZ) and [18F] flumazenil ([18F]FMZ). Methods: PET acquisitions were performed on a small-animal scanner following injection of [18F]FFMZ in nine rats and [18F]FMZ in eight rats. The following treatments were investigated: (1) injection of the tracer dose, (2) presaturation then injection of the tracer dose, and (3) injection of the tracer dose followed by a displacement injection. Unchanged tracer was measured in plasma and brain structures in four animals 10 and 30 min after injection, and ex-vivo autoradiography was also performed. Results: For both [18F]FFMZ and [18F]FMZ maximal brain activity peaked rapidly, and was highest in the hippocampus (1.12±0.06 SUV, 1.24±0.10 SUV, respectively), and lowest in the pons (1.00±0.07 SUV, 1.03±0.09 SUV, respectively). By 50 min after injection, maximal uptake for [18F]FFMZ and [ 18F]FMZ had decreased in the hippocampus to 18±3% and 80±1% (p<0.01), respectively. The presaturation and displacement studies showed a higher nonspecific component for [18F]FFMZ than for [18F]FMZ. Metabolite studies showed that at 30 min only 10% of the signal was from [18F]FFMZ in the brain. This nonspecific binding was apparent on autoradiography. In contrast, [18F]FMZ accounted for >70% of the signal in the brain, which resulted in well-defined regional binding on autoradiography. Conclusion: These results demonstrate that [ 18F]FMZ is a superior radiotracer to [18F]FFMZ for in-vivo PET imaging of the GABAA/cBZR, having slower metabolism and leading to lower concentrations of metabolites in the brain that results in a substantially better signal-to-noise ratio.

Original languageEnglish
Pages (from-to)958-965
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number6
Publication statusPublished - Jun 2009
Externally publishedYes


  • Flumazenil
  • GABA/cBZ receptor
  • PET
  • Radioligand
  • Rat

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