The Acute and Early Effects of Whole-Brain Irradiation on Glial Activation, Brain Metabolism, and Behavior: a Positron Emission Tomography Study

PURPOSE: 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. PROCEDURES: Rats underwent 0-, 10-, or 25-Gy whole-brain irradiation. At 3 and 31 days post irradiation, 1-(2-chlorophenyl)-N-[(11)C]methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([(11)C]PK11195) and 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)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. RESULTS: Twenty-five-gray-irradiated rats showed higher [(11)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 [(11)C]PK11195 uptake than controls and 10-Gy-irradiated group (p < 0.05). Within-group analysis showed that [(11)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 [(18)F]FDG uptake on day 3 (p < 0.05). [(18)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. CONCLUSIONS: Non-invasive PET imaging indicated that brain irradiation induces neuroinflammation and a metabolic flare, without causing acute or early-delayed behavioral changes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11307-020-01483-y) contains supplementary material, which is available to authorized users.