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Abstract #0284

Hyperpolarized [1-13C]-alanine monitors tumor immortality and detects response to therapy in patient-derived glioblastoma models in vivo

Georgios Batsios1, Meryssa Tran1, Anne Marie Gillespie1, Celine Taglang1, Sabrina Ronen1, Joseph Costello2, and Pavithra Viswanath1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

Synopsis

Telomerase reverse transcriptase (TERT) expression is essential for tumor proliferation. TERT also reprograms metabolism by elevating NADH and upregulating the alanine transporter ASCT2. Here, we exploit these TERT-associated metabolic alterations for non-invasive imaging in live GBM cells and orthotopic tumors using hyperpolarized [1-13C]-alanine. Combined treatment with the TERT inhibitor 6-thio-2’-deoxyguanosine and the ASCT2 inhibitor V-9302 inhibits GBM proliferation, identifying a novel therapeutic opportunity. Importantly, lactate production from hyperpolarized [1-13C]-alanine is an early biomarker of response to treatment in vivo, prior to the onset of anatomical alterations. Our findings pave the way for improved therapy and response assessment for GBM patients.

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Abstract