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Deuterium magnetic resonance spectroscopy using 2H-pyruvate allows non-invasive in vivo imaging of TERT expression in brain tumors
Georgios Batsios1, Celine Taglang1, Meryssa Tran1, Anne Marie Gillespie1, Joseph Costello2, Sabrina Ronen1, and Pavithra Viswanath1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Neurological Surgery, UCSF, San Francisco, CA, United States
Telomerase reverse transcriptase (TERT) is essential for glioma proliferation and is an attractive therapeutic target. Here, we show that TERT expression in gliomas is linked to higher NADH, an effect that can be non-invasively monitored by deuterium metabolic imaging using [U-2H]pyruvate.
Lactate production from [U-2H]pyruvate is localized to the tumor region in vivo. (A) Anatomical T2-weighted MRI of a mouse bearing an orthotopic BT88 tumor xenograft. Representative 2H-MR spectra from contralateral normal brain (B) and tumor (C) voxels at the first time point after injection of [U-2H]pyruvate in a mouse bearing an orthotopic BT88 tumor. Metabolic heatmap of the SNR of lactate (D) and the ratio of lactate to post-injection HDO (E) in mouse bearing an orthotopic BT88 tumor. The tumor is delineated by white line.
Lactate production from [U-2H]pyruvate is higher in orthotopic glioma-bearing mice in vivo. Lactate signal normalized to the ratio of post-injection HDO at each time point to pre-injection HDO is higher in mice bearing orthotopic glioma xenografts relative to tumor-free controls. ** refers to p<0.01, *** refers to p<0.001.