Visualizing reactive astrogliosis extends survival in glioblastoma patients

Glioblastoma is a devastating brain tumor with dismal prognosis of only 15-month survival regardless of surgical resection with few alternatives. Here, we report a reactive astrogliosis-targeted neuroimaging technique using the fusion of 11C-acetate PET and MRI (AcePET) extended the overall survival of patients by 5.25 months compared to conventional MRI-guided surgery. Targeted biopsy of 11C-acetate uptake-increased regions showed the signs of reactive astrogliosis with cancer stem cells at the boundary of high-grade gliomas. The appearance of marginal reactive astrogliosis and MCT1-dependent 11C-acetate uptake was recapitulated in U87MG-orthotophic models. U87MG-derived excessive glutamate caused reactive astrogliosis and aberrant astrocytic GABA-release, which subsequently reduced neuronal glucose uptake through glucose transporter-3 (GLUT3). We propose AcePET-guided surgery, visualizing reactive astrogliosis, as an advanced surgical strategy to improve glioblastoma patient survival. One-Sentence Summary AcePET-guided surgery extends patient survival by visualizing reactive astrogliosis at the tumor margin ### Competing Interest Statement The authors have declared no competing interest.