Glioma-associated microglia and macrophages (GAMMs) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony-stimulating factor 1 receptor (CSF-1R). We applied noninvasive PET/CT and PET/MRI using ¹⁸F-fluoroethyltyrosine (¹⁸F-FET) (amino acid metabolism) and N,N-diethyl-2-[4-(2-¹⁸F-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (¹⁸F-DPA-714) (translocator protein) to understand the role of GAMMs in glioma initiation, monitor in vivo therapy-induced GAMM depletion, and observe GAMM repopulation after drug withdrawal. Methods: C57BL/6 mice (n = 44) orthotopically implanted with syngeneic mouse GL261 glioma cells were treated with different regimens using the CSF-1R inhibitor PLX5622 (6-fluoro-N-((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine) or vehicle, establishing a preconditioning model and a repopulation model, respectively. The mice underwent longitudinal PET/CT and PET/MRI. Results: The preconditioning model indicated similar tumor growth based on MRI (44.5% ± 24.8%), ¹⁸F-FET PET (18.3% ± 11.3%), and ¹⁸F-DPA-714 PET (16% ± 19.04%) volume dynamics in all groups, suggesting that GAMMs are not involved in glioma initiation. The repopulation model showed significantly reduced ¹⁸F-DPA-714 uptake (–45.6% ± 18.4%), significantly reduced GAMM infiltration even after repopulation, and a significantly decreased tumor volume (–54.29% ± 8.6%) with repopulation as measured by MRI, supported by a significant reduction in ¹⁸F-FET uptake (–50.2% ± 5.3%). Conclusion: ¹⁸F-FET and ¹⁸F-DPA-714 PET/MRI allow noninvasive assessment of glioma growth under various regimens of CSF-1R therapy. CSF-1R–mediated modulation of GAMMs may be of high interest as therapy or cotherapy against glioma.

胶质瘤相关的小胶质细胞和巨噬细胞 (GAMM) 是创造免疫抑制微环境的关键参与者。通过抑制集落刺激因子 1 受体 (CSF-1R)，可以有效地靶向它们。我们使用¹⁸ F-氟乙基酪氨酸 ( ¹⁸ F-FET)（氨基酸代谢）和N,N -二乙基-2-[4-(2- ¹⁸ F-氟乙氧基)苯基]-5应用非侵入性 PET/CT 和 PET/MRI ,7-二甲基吡唑并[1,5- a ]嘧啶-3-乙酰胺 ( ¹⁸ F-DPA-714)（转运蛋白）以了解 GAMM 在神经胶质瘤起始中的作用，监测体内治疗诱导的 GAMM 消耗，并观察 GAMM停药后重新种群。方法： C57BL/6 小鼠（n= 44) 使用 CSF-1R 抑制剂 PLX5622（6-fluoro- N -((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-( (5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine) 或载体，分别建立预处理模型和再增殖模型。小鼠接受纵向 PET/CT 和 PET/MRI。结果：预处理模型显示基于 MRI (44.5% ± 24.8%)、¹⁸ F-FET PET (18.3% ± 11.3%) 和¹⁸ F-DPA-714 PET (16% ± 19.04%) 体积动力学的相似肿瘤生长在所有组中，表明 GAMM 不参与神经胶质瘤的发生。重新填充模型显示显着减少¹⁸F-DPA-714 摄取 (–45.6% ± 18.4%)，即使在重新填充后也显着减少 GAMM 浸润，并且通过 MRI 测量的重新填充后肿瘤体积显着减少 (–54.29% ± 8.6%)，这得到显着减少的支持¹⁸ F-FET 吸收 (–50.2% ± 5.3%)。结论： ¹⁸ F-FET 和¹⁸ F-DPA-714 PET/MRI 允许在各种 CSF-1R 治疗方案下对神经胶质瘤生长进行无创评估。CSF-1R 介导的 GAMM 调节作为神经胶质瘤的治疗或联合疗法可能具有很高的吸引力。