Altered glutamate signaling is thought to be involved in a myriad of psychiatric disorders. Positron emission tomography (PET) imaging with [¹⁸F]FPEB allows assessing dynamic changes in metabotropic glutamate receptor 5 (mGluR5) availability underlying neuropathological conditions. The influence of endogenous glutamatergic levels into receptor binding has not been well established yet. The purpose of this study was to explore the [¹⁸F]FPEB binding regarding to physiological fluctuations or acute changes of glutamate synaptic concentrations by a translational approach; a PET/MRS imaging study in 12 healthy human volunteers combined to a PET imaging after an N-acetylcysteine (NAc) pharmacological challenge in rodents. No significant differences were observed with small-animal PET in the test and retest conditions on the one hand and the NAc condition on the other hand for any regions. To test for an interaction of mGuR5 density and glutamatergic concentrations in healthy subjects, we correlated the [¹⁸F]FPEB BP_ND with Glu/Cr, Gln/Cr, Glx/Cr ratios in the anterior cingulate cortex VOI; respectively, no significance correlation has been revealed (Glu/Cr: r = 0.51, p = 0.09; Gln/Cr: r = −0.46, p = 0.13; Glx/Cr: r = −0.035, p = 0.92).These data suggest that the in vivo binding of [¹⁸F]FPEB to an allosteric site of the mGluR5 is not modulated by endogenous glutamate in vivo. Thus, [¹⁸F]FPEB appears unable to measure acute fluctuations in endogenous levels of glutamate.

谷氨酸信号的改变被认为与多种精神疾病有关。[ ¹⁸ F] FPEB的正电子发射断层扫描（PET）成像可评估神经病理学状况下代谢型谷氨酸受体5（mGluR5）可用性的动态变化。内源性谷氨酸能水平对受体结合的影响尚未很好地建立。这项研究的目的是探索[ ¹⁸F] FPEB通过翻译方法与谷氨酸突触浓度的生理波动或急性变化有关；一项针对12位健康人类志愿者的PET / MRS影像学研究与在啮齿动物中进行N-乙酰半胱氨酸（NAc）药理学挑战后的PET影像学相结合。对于任何区域，一方面在测试和重新测试条件下，另一方面在NAc条件下，小动物PET均未观察到显着差异。为了测试健康受试者中mGuR5密度和谷氨酸能浓度的相互作用，我们将[ ¹⁸ F] FPEB BP _ND与前扣带回VOI中的Glu / Cr，Gln / Cr，Glx / Cr比值相关联。分别没有显着性相关性揭示（Glu / Cr：r  = 0.51，p = 0.09; Gln / Cr：r  ＝ -0.46，p  ＝ 0.13。Glx / Cr：r  = -0.035，p  = 0.92）。这些数据表明[ ¹⁸ F] FPEB与mGluR5变构位点的体内结合不受体内内源谷氨酸的调节。因此，[ ¹⁸ F] FPEB似乎无法测量内源性谷氨酸水平的剧烈波动。