TY - JOUR T1 - Visualizing cancer-originated acetate uptake through MCT1 in reactive astrocytes demarcates tumor border and extends survival in glioblastoma patients JF - bioRxiv DO - 10.1101/2021.04.13.439750 SP - 2021.04.13.439750 AU - Hae Young Ko AU - Jee-In Chung AU - Dongwoo Kim AU - Yongmin Mason Park AU - Han Hee Jo AU - Sangwon Lee AU - Seon Yoo Kim AU - Jisu Kim AU - Joong-Hyun Chun AU - Kyung-Seok Han AU - Misu Lee AU - Yeonha Ju AU - Sun Jun Park AU - Ki Duk Park AU - Min-Ho Nam AU - Youngjoo Park AU - Se Hoon Kim AU - Jin-Kyoung Shim AU - Seok-Gu Kang AU - Jong Hee Chang AU - C. Justin Lee AU - Mijin Yun Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/22/2021.04.13.439750.abstract N2 - Glioblastoma multiforme (GBM) is a devastating brain tumor with dismal prognosis of only 15-month survival regardless of surgical resection. Here, we report an advanced neuroimaging technique combining 11C-acetate PET and MRI (AcePET), visualizing the boundary beyond the MRI-defined tumor. Targeted biopsy of the regions with increased 11C-acetate uptake revealed the presence of reactive astrocytes with enhanced acetate-transporter MCT1, along with cancer stem cells. Reactive astrogliosis and MCT1-dependent 11C-acetate-uptake were recapitulated in U87MG-orthotopic models. Mechanistically, glycolytic tumor cells release excessive acetate causing reactive astrogliosis, leading to the release of aberrant astrocytic GABA and H2O2, which further down-regulate the neuronal glucose uptake through GLUT3. Clincally, AcePET-guided surgery allows complete tumor resection of infiltrating cancer stem cells and extends the overall survival of patients by 5.25 months compared to conventional MRI-guided surgery. We established a new concept of the metabolic interactions between GBM cells and neighboring neurons through reactive astrocytes and developed AcePET-guided surgery to fight against GBM.Competing Interest StatementThe authors have declared no competing interest. ER -