Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mol Imaging Biol. 2020 Aug;22(4):1012-1020. doi: 10.1007/s11307-020-01483-y.
Radiotherapy is a frequently applied treatment modality for brain tumors. Concomitant irradiation of normal brain tissue can induce various physiological responses. The aim of this study was to investigate whether acute and early-delayed effects of brain irradiation on glial activation and brain metabolism can be detected with positron emission tomography (PET) and whether these effects are correlated with behavioral changes.
Rats underwent 0-, 10-, or 25-Gy whole-brain irradiation. At 3 and 31 days post irradiation, 1-(2-chlorophenyl)-N-[C]methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([C]PK11195) and 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) PET scans were acquired to detect changes in glial activation (neuroinflammation) and glucose metabolism, respectively. The open-field test (OFT) was performed on days 6 and 27 to assess behavioral changes.
Twenty-five-gray-irradiated rats showed higher [C]PK11195 uptake in most brain regions than controls on day 3 (striatum, hypothalamus, accumbens, septum p < 0.05), although some brain regions had lower uptake (cerebellum, parietal association/retrosplenial visual cortex, frontal association/motor cortex, somatosensory cortex, p < 0.05). On day 31, several brain regions in 25-Gy-irradiated rats still showed significantly higher [C]PK11195 uptake than controls and 10-Gy-irradiated group (p < 0.05). Within-group analysis showed that [C]PK11195 uptake in individual brain regions of 25-Gy treated rats remained stable or slightly increased between days 3 and 31. In contrast, a significant reduction (p < 0.05) in tracer uptake between days 3 and 31 was found in all brain areas of controls and 10-Gy-irradiated animals. Moreover, 10-Gy treatment led to a significantly higher [F]FDG uptake on day 3 (p < 0.05). [F]FDG uptake decreased between days 3 and 31 in all groups; no significant differences between groups were observed anymore on day 31, except for increased uptake in the hypothalamus in the 10-Gy group. The OFT did not show any significant differences between groups.
Non-invasive PET imaging indicated that brain irradiation induces neuroinflammation and a metabolic flare, without causing acute or early-delayed behavioral changes.
放射疗法是治疗脑肿瘤的常用方法。同时照射正常脑组织会引起各种生理反应。本研究的目的是探讨脑照射后急性和早期延迟对神经胶质激活和脑代谢的影响是否可以通过正电子发射断层扫描（PET）检测，以及这些影响是否与行为变化相关。
大鼠接受 0、10 或 25-Gy 全脑照射。在照射后 3 和 31 天，进行 1-（2-氯苯基）-N-[C]甲基-（1-甲基丙基）-3-异喹啉羧酰胺（[C]PK11195）和 2-脱氧-2-[F]氟-D-葡萄糖（[F]FDG）PET 扫描，以分别检测神经胶质激活（神经炎症）和葡萄糖代谢的变化。在第 6 天和第 27 天进行开放式场测试（OFT）以评估行为变化。
25-Gy 照射的大鼠在第 3 天（纹状体、下丘脑、伏隔核、隔区，p<0.05）大多数脑区的 [C]PK11195 摄取高于对照组，但一些脑区的摄取较低（小脑、顶叶联合/ retrosplenial 视觉皮层、额叶联合/运动皮层、躯体感觉皮层，p<0.05）。在第 31 天，25-Gy 照射组的几个脑区仍显示出比对照组和 10-Gy 照射组更高的 [C]PK11195 摄取（p<0.05）。组内分析显示，25-Gy 处理大鼠个别脑区的 [C]PK11195 摄取在第 3 天至第 31 天之间保持稳定或略有增加。相比之下，对照组和 10-Gy 照射动物所有脑区的示踪剂摄取在第 3 天至第 31 天之间显著减少（p<0.05）。此外，10-Gy 处理导致第 3 天 [F]FDG 摄取增加（p<0.05）。所有组的 [F]FDG 摄取在第 3 天至第 31 天之间下降；第 31 天各组之间不再观察到显著差异，除了 10-Gy 组下丘脑的摄取增加。OFT 未显示组间任何差异。
非侵入性 PET 成像表明，脑照射会引起神经炎症和代谢亢进，而不会引起急性或早期延迟的行为变化。
