The positron emission tomography probes 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[¹⁸F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([¹⁸F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes’ accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [¹⁴C]2DG and [¹⁸F]BCPP-EF to give a new insight into the hypothesis that different uptake of [¹⁸F]FDG and [¹⁸F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation. LPS or IL4 stimulation increased the proinflammatory or anti-inflammatory marker gene expression in microglial cells. In LPS-stimulated cells, [¹⁴C]2DG uptake and glycolysis related gene expression were elevated, and [¹⁸F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [¹⁸F]BCPP-EF uptake was increased, and [¹⁴C]2DG uptake was decreased. The expression of genes involved in glycolysis and mitochondrial complex I subunits was not changed by IL4 stimulation. The uptake of [¹⁴C]2DG and [¹⁸F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [¹⁸F]FDG and [¹⁸F]BCPP-EF can be influenced by the different aspects of neuroinflammation.

正电子发射断层扫描探针 2-脱氧-2-[ ¹⁸ F]氟-D-葡萄糖 ([ ¹⁸ F]FDG) 和 2-叔丁基-4-氯-5-{6-[2-(2-[ ¹⁸ F]氟乙氧基)-乙氧基]-吡啶-3-基甲氧基}-2H-哒嗪-3-酮 ([ ¹⁸ F]BCPP-EF) 设计用于分别评估糖酵解和氧化磷酸化，并且均用于估计神经元活动。然而，之前的研究表明，这些探针在受损区域的积累存在差异，可能是由于存在类似于有害或神经保护表型的激活的小胶质细胞。因此，我们评估了脂多糖 (LPS) 和白细胞介素 4 (IL4) 刺激的小胶质细胞对 [ ¹⁴ C]2DG 和 [ ^{18 F]BCPP-EF 的摄取，以对 [ 18} F]FDG的不同摄取的假设提供新的见解[ ¹⁸ F]BCPP-EF可归因于小胶质细胞激活期间激活的不同代谢途径。LPS 或 IL4 刺激增加了小胶质细胞中促炎或抗炎标记基因的表达。在LPS刺激的细胞中，[ ¹⁴ C]2DG摄取和糖酵解相关基因表达升高，并且[ ¹⁸ F]BCPP-EF摄取减少。在IL4刺激的细胞中，[ ¹⁸ F]BCPP-EF摄取增加，并且[ ¹⁴ C]2DG摄取减少。IL4 刺激不会改变参与糖酵解和线粒体复合物 I 亚基的基因表达。LPS 和 IL4 刺激的极化小胶质细胞对[ ¹⁴ C]2DG 和 [ ¹⁸ F]BCPP-EF的摄取不同。目前的结果表明，代谢示踪剂[ ¹⁸ F]FDG 和[ ¹⁸ F]BCPP-EF 的体内积累可能受到神经炎症不同方面的影响。