European Journal of Nuclear Medicine and Molecular Imaging

, 36:958

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
Original Article

DOI: 10.1007/s00259-009-1066-4

Cite this article as:
Dedeurwaerdere, S., Gregoire, M., Vivash, L. et al. Eur J Nucl Med Mol Imaging (2009) 36: 958. doi:10.1007/s00259-009-1066-4

Abstract

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.

Keywords

RadioligandFlumazenilPETRatGABAA/cBZ receptor

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Stefanie Dedeurwaerdere
    • 1
    • 2
  • Marie-Claude Gregoire
    • 2
  • Lucy Vivash
    • 1
  • Peter Roselt
    • 3
  • David Binns
    • 3
  • Christopher Fookes
    • 2
  • Ivan Greguric
    • 2
  • Tien Pham
    • 2
  • Christian Loc’h
    • 2
  • Andrew Katsifis
    • 2
  • Rodney J. Hicks
    • 3
  • Terence J. O’Brien
    • 1
  • Damian E. Myers
    • 1
  1. 1.Department of Medicine (RMH)University of MelbourneParkvilleAustralia
  2. 2.Radiopharmaceuticals Research InstituteANSTOSydneyAustralia
  3. 3.Centre for Molecular ImagingPeter MacCallum Cancer CentreMelbourneAustralia