Dedeurwaerdere Stefanie, Gregoire Marie-Claude, Vivash Lucy, Roselt Peter, Binns David, Fookes Christopher, Greguric Ivan, Pham Tien, Loc'h Christian, Katsifis Andrew, Hicks Rodney J, O'Brien Terence J, Myers Damian E
Department of Medicine (RMH), University of Melbourne, Royal Parade, Parkville, Victoria, Australia.
Eur J Nucl Med Mol Imaging. 2009 Jun;36(6):958-65. doi: 10.1007/s00259-009-1066-4. Epub 2009 Feb 10.
[(11)C]Flumazenil shows promise as a clinical and research PET radiotracer to image changes in GABA(A) central benzodiazepine receptor (cBZR), but its widespread use has been limited by practical limitations of [(11)C]. This study evaluated the imaging characteristics of two fluorinated PET radiotracers in rats in vivo: [(18)F]fluoroflumazenil ([(18)F]FFMZ) and [(18)F]flumazenil ([(18)F]FMZ).
PET acquisitions were performed on a small-animal scanner following injection of [(18)F]FFMZ in nine rats and [(18)F]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.
For both [(18)F]FFMZ and [(18)F]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 [(18)F]FFMZ and [(18)F]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 [(18)F]FFMZ than for [(18)F]FMZ. Metabolite studies showed that at 30 min only 10% of the signal was from [(18)F]FFMZ in the brain. This nonspecific binding was apparent on autoradiography. In contrast, [(18)F]FMZ accounted for >70% of the signal in the brain, which resulted in well-defined regional binding on autoradiography.
These results demonstrate that [(18)F]FMZ is a superior radiotracer to [(18)F]FFMZ for in-vivo PET imaging of the GABA(A)/cBZR, having slower metabolism and leading to lower concentrations of metabolites in the brain that results in a substantially better signal-to-noise ratio.
[（11）C]氟马西尼作为一种用于成像γ-氨基丁酸A（GABA A）中枢苯二氮䓬受体（cBZR）变化的临床及研究用正电子发射断层扫描（PET）放射性示踪剂显示出应用前景，但其广泛应用受到[（11）C]实际局限性的限制。本研究评估了两种氟化PET放射性示踪剂在大鼠体内的成像特性：[（18）F]氟氟马西尼（[（18）F]FFMZ）和[（18）F]氟马西尼（[（18）F]FMZ）。
对9只注射[（18）F]FFMZ和8只注射[（18）F]FMZ的大鼠在小动物扫描仪上进行PET采集。研究了以下处理：（1）注射示踪剂剂量；（2）预饱和后注射示踪剂剂量；（3）注射示踪剂剂量后进行置换注射。在注射后10分钟和30分钟，对4只动物的血浆和脑结构中未变化的示踪剂进行测量，并进行离体放射自显影。
对于[（18）F]FFMZ和[（18）F]FMZ，脑内最大活性均迅速达到峰值，在海马体中最高（分别为1.12±0.06标准摄取值（SUV）和1.24±0.10 SUV），在脑桥中最低（分别为1.00±0.07 SUV和1.03±0.09 SUV）。注射后50分钟时，[（18）F]FFMZ和[（18）F]FMZ在海马体中的最大摄取量分别降至18±3%和80±1%（p<0.01）。预饱和和置换研究显示，[（18）F]FFMZ的非特异性成分高于[（18）F]FMZ。代谢物研究表明，在30分钟时，脑内仅10%的信号来自[（18）F]FFMZ。这种非特异性结合在放射自显影中很明显。相比之下，[（18）F]FMZ在脑中占信号的>70%，这导致放射自显影上有明确的区域结合。
这些结果表明，对于GABA A/cBZR的体内PET成像，[（18）F]FMZ是比[（18）F]FFMZ更优的放射性示踪剂，其代谢较慢，导致脑内代谢物浓度较低，从而产生明显更好的信噪比。
