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

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. © 2009, Springer.
Rats, Radiopharmaceuticals, Tracer techniques, In vivo, Positron computed tomography, Fluorination
Dedeurwaerdere, S.,Grégoire , M. C., Vivash, L., Roselt, P., Binns, D., Fookes, C., Greguric, I., Pham, T., Loc'h, C., Katsifis, A., Hicks, R. J., O'Brien, T. J., & Myers, D. E. (2009). In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat. European Journal of Nuclear Medicine and Molecular Imaging, 36(6), 958-965. doi:10.1007/s00259-009-1066-4