Kumar Pichumani^1,2, Omkar B Ijare¹, Suzanne Powell³, and David S Baskin^1,2
1Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX, United States, ²Weill Cornell Medical College, New York, NY, United States, ³Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX, United States

Normal brain switches to utilization of ketone bodies only during prolonged starvation. It is not known whether brain tumors can utilize ketone body under in vivo conditions. There are ongoing clinical trials on using ketogenic diet as adjuvant therapy for the treatment of brain tumors. Here, we show that brain tumors (meningioma and GBM) can fully oxidize ketone body and therefore ketogenic diet may not be effective in the treatment of these tumor patients. MCT1 is involved in the transport of BHB into tumor cells and therefore it is feasible to target BHB metabolism using MCT1 inhibitor.

Georgios Batsios¹, Meryssa Tran¹, Anne Marie Gillespie¹, Celine Taglang¹, Sabrina Ronen¹, Joseph Costello², and Pavithra Viswanath^1
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

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.

Noriaki Minami¹, Donghyun Hong¹, Nicholas Stevers², Carter J Barger², Georgios Batsios¹, Anne Marie Gillespie¹, Joseph F Costello², Pavithra Viswanath¹, and Sabrina M Ronen^1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Department of Neurological Surgery, UCSF, San Francisco, CA, United States

Telomerase reverse transcriptase (TERT) expression results from TERT promoter mutations and is a hallmark of cancer. GABPB1, its upstream transcriptional factor, was recently identified as a promising tumor-specific therapeutic target. However, imaging methods that can detect TERT expression and its inhibition with emerging GABPB1-based therapeutics are limited. Here, we demonstrate that the combination of ¹H-MRS and hyperpolarized ¹³C-MRS of [1-¹³C]pyruvate allow detection of TERT modulation in TERT-expressing GBM cells and in vivo tumors. These findings could be translated to the clinic and thus improve the monitoring and personalized treatment of GBM.

Wufan Zhao¹, Eduardo Coello¹, Vicky Liao¹, Assaf Tal², and Alexander Lin^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Chemical & Biological Physics, Weizmann Institute of Science, Rehovot, Israel

This work fuses manual segmentation of T2/FLAIR hyperintensity regions using 3D Slicer with multivoxel magnetic resonance spectroscopy (MRSI), which profiles neurochemical concentrations in a wide area of the brain. The utility of MRSI is demonstrated in the mapping of metabolites including 2HG, N-acetyl aspartate, myoinositol, glutamate plus glutamine, lactate, and choline in the region of interest. Voxel fractions of hyperintensity were correlated to metabolites, and metabolite-to-creatine ratio intercepts were used to compare hyperintense with healthy tissue.

Arjan D. Hendriks¹, Andor Veltien², Ingmar J. Voogt³, Arend Heerschap², Tom W.J. Scheenen², and Jeanine J. Prompers^1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Department of Medical Imaging (Radiology), Radboud University Medical Center, Nijmegen, Netherlands, ³WaveTronica B.V., Utrecht, Netherlands

The worldwide increase in sugar consumption is a major health concern. The contribution of fructose to the epidemic of metabolic disorders is controversial. This study investigated differences between glucose and fructose metabolism in the liver using dynamic deuterium metabolic imaging (DMI). Deuterium signal time curves after bolus injection and slow infusion were successfully acquired and showed different patterns. It was found that the peak concentration and conversion of deuterated glucose was different from that of fructose, indicating faster turnover of the latter. Overall, these methods could potentially lead to better understanding of healthy liver metabolism and aberrations in metabolic diseases.

Tao Lin¹, Jiazheng Wang², Liangjie Lin², Lihua Chen ¹, Qingwei Song¹, Renwang Pu¹, Ying Zhao¹, Xue Ren¹, Qihao Xu¹, and Ailian Liu^1
1The First Affiliated Hospital of Dalian Medical University, Dalian, China, ²Philips Healthcare, Beijing, China

Differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the most common types of primary liver cancer, is important for the treatment planning and prognosis, but remains challenging via conventional radiological tools. Results by this study indicated that both mDIXON Quant and IVIM parameters showed significant different between HCC and ICC groups, and their combination can be of great potential value for clinical differential diagnosis between the two lesions.

Upasana Roy¹, Elise Y. Lepicard¹, Jessica K.R. Boult¹, Carol Box¹, Kevin J. Harrington¹, James P.B. O’Connor¹, Yann Jamin¹, and Simon P. Robinson^1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, United Kingdom

Oxygen-enhanced (OE)-MRI was used to map and quantify hypoxia (pOxyR) in two murine models of oral cavity squamous cell carcinoma, a tumour type in which hypoxia adversely affects patient prognosis. OE-MRI relies on quantifying changes in the longitudinal MRI relaxation rate R₁ induced by excess paramagnetic oxygen molecules dissolved in blood plasma and interstitial fluid with inhalation of oxygen. When combined with susceptibility-contrast MRI for determination of fractional blood volume and diffusion-weighted MRI to assess cellularity, OE-MRI enables an assessment of the spatial distribution and extent of tumour hypoxia, patent vasculature and necrosis.

Michael J Dubec^1,2, Anubhav Datta^1,3, Ross A Little¹, Abigael Clough⁴, David L Buckley^2,5, Christina Hague⁶, Damien McHugh^1,2, Michael Berks¹, Susan Cheung¹, Amal Salah⁷, David Higgins⁸, Cynthia L Eccles^1,4, Robert Bristow^1,6, Josephine H Naish^9,10, Julian C Matthews¹¹, Peter Hoskin^1,6,12, Marcel van Herk¹, Geoff JM Parker^10,13, Ananya Choudhury^1,6, Andrew McPartlin⁶, and James PB O'Connor^1,3,14
1Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, ²Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, United Kingdom, ³Radiology, The Christie NHS Foundation Trust, Manchester, United Kingdom, ⁴Radiotherapy, The Christie NHS Foundation Trust, Manchester, United Kingdom, ⁵Biomedical Imaging, University of Leeds, Leeds, United Kingdom, ⁶Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom, ⁷Proton Beam Therapy, The Christie NHS Foundation Trust, Manchester, United Kingdom, ⁸Philips, Manchester, United Kingdom, ⁹MCMR, University of Manchester NHS Foundation Trust, Manchester, United Kingdom, ¹⁰Bioxydyn Ltd, Manchester, United Kingdom, ¹¹Neuroscience and Experimental Psychology, University of Manchester, Manchester, United Kingdom, ¹²Radiotherapy, Mount Vernon, London, United Kingdom, ¹³Centre for Medical Image Computing, Unversity College London, London, United Kingdom, ¹⁴Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom

Tumour hypoxia is associated with poor treatment outcome, tumour progression and treatment resistance. Oxygen-enhanced (OE)-MRI has shown promise as a non-invasive method for mapping and quantifying hypoxia. We demonstrate, for the first time, the application of the OE-MRI technique in patients with head and neck carcinoma to monitor changes in hypoxia due to treatment, and translate the technique onto an MR Linac system, demonstrating feasibility in a first-in-human study.