TY - JOUR T1 - Single dose whole brain irradiation causes glial activation and increased cerebral blood flow in rats: a longitudinal PET/SPECT imaging study JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 184 LP - 184 VL - 60 IS - supplement 1 AU - Elisa Maciel AU - Andrea Parente AU - Janine Doorduin AU - Erik de Vries Y1 - 2019/05/01 UR - http://jnm.snmjournals.org/content/60/supplement_1/184.abstract N2 - 184Objectives: Whole brain irradiation, despite being an important therapy for brain tumor patients, can lead to impairment in brain function, often presenting as memory and attention loss. The specific mechanisms involved in this damage are not yet fully understood, but seem to be related to a neuroinflammatory response to irradiation. Through Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), our study aimed to investigate the effects of irradiation in the normal rat brain, particularly regarding microglial activation and cerebral blood flow - both parameters related to neuroinflammation. Materials and Methods: Male Wistar rats (n=8 per group) subjected to 25 Gy X-ray radiation and controls were submitted to 11C-PK1195 PET imaging to assess microglial activation or 99mTc-HMPAO SPECT imaging to assess cerebral blood flow. 11C-PK1195 PET scans were performed at baseline and at 1, 3, 5, 9, 12, 59 and 88 days after irradiation. The 99mTc-HMPAO SPECT scans, on the other hand, were performed at baseline and at 1, 3, 5, 9, 60 and 90 days after irradiation. The Generalized Estimating Equations (GEE) model was used for statistical analysis of the data. Results: Irradiated animals showed a significant increase in 11C-PK1195 uptake in all the specific brain regions and in the whole brain (36%, p<0.001) on day 12. The percentage increase was significantly higher in non-cortical than in cortical regions (p<0.001). The increase did not persist, and the uptake had normalized to baseline values on days 59 and 88. In addition, irradiated animals showed a gradual increase in 99mTc-HMPAO uptake, which was significant from day 5 onwards in most brain regions and in the whole brain (42%, p=0.003). In later timepoints, the uptake kept on increasing, being the highest on day 90 amongst the analyzed timepoints (87%, p<0.001). Conclusions: Whole brain irradiation induced an acute and transient increase in microglial activation in rats, more expressive in non-cortical brain regions. In addition, the whole brain irradiation also induced a progressive increase in cerebral blood flow, which is already significant in the acute phase but even higher in later timepoints. Our study therefore supports the hypothesis that neuroinflammation is involved in impairment following brain irradiation. ER -