Santosh K Bharti¹, Louis Dore-Savard¹, Aleksander S Popel², and Zaver M Bhujwalla^1
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Division of Cancer Imaging Research, Baltimore, MD, United States, ²Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Systems Biology Laboratory, Baltimore, MD, United States

Interstitial fluid (IF) is a key component of the tumor microenvironment (TME) that encompasses the secretome and holds the key to several of the phenotypic traits of cancer.  Modern analytical methods like 1H MR spectroscopy (MRS) allow for comprehensive metabolic characterization of tissue, cell, and bio-fluids content to better understand the TME and cancer metabolism. Here, for the first time, we have metabolically characterized TIF from triple negative and estrogen receptor (ER)-positive human breast tumor xenografts with or without VEGF overexpression and detected significant differences between tumor types and with VEGF overexpression.    

Yan Lin¹, Changchun Ma², Zhening Wang¹, Zhiwei Shen¹, and Renhua Wu^1
1Radiology Department, Second Affiliated Hospital, Shantou University Medical College, Shantou City, China, People's Republic of, ²Radiation Oncology, Cancer Hospital, Shantou University Medical College, Shantou City, China, People's Republic of

Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its earlier detection for optimal disease management.This study aimed to validate the ability of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients.Our findings revealed that the fecal metabolic profiles of healthy controls can be distinguished from CRC patients, even in the early stage (stage I/II), highlighting the potential utility of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients.

James R Larkin¹, Alex M Dickens², Timothy D W Claridge³, Daniel C Anthony², and Nicola R Sibson^1
1CRUK and MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom, ²Department of Pharmacology, University of Oxford, Oxford, United Kingdom,³Department of Chemistry, University of Oxford, Oxford, United Kingdom

Secondary tumours, or metastases, in the brain are currently detected at a late stage by gadolinium-enhanced MRI. We used mouse models of brain metastases, coupled with high resolution NMR of urine to identify characteristic patterns of metabolites in tumour-bearing animals. A model with a tumour cells implanted directly in the brain showed sensitive and specific detection at day 5 with increasing separation at later time points. Models injecting cells into the heart or venous circulation give rise to differing systemic and central nervous system (CNS) tumour burdens. Metabolite patterns allow identification of these animals with a heavy CNS tumour burden.

Ilwoo Park¹, Rintaro Hashizume², Joanna Phillips^3,4, Sabine Mueller^3,5, and Sarah Nelson^1,6
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery, Northwestern University, Chicago, IL, United States, ³Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, ⁴Pathology, University of California San Francisco, San Francisco, CA, United States, ⁵Pediatrics, University of California San Francisco, San Francisco, CA, United States, ⁶Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States

Diffuse intrinsic pontine gliomas (DIPGs) are one of the most difficult pediatric cancers to treat. This study investigated the feasibility of ¹³C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized (HP) [1-¹³C]pyruvate for differentiating molecular characteristics of DIPGs. Differences in the lactate signal that were observed in two distinct biopsy-originated orthotopic DIPG tumors were associated with changes in the levels of LHDA and HIF-1α activity. This suggests that the non-invasive characterization of DIPGs using this new neuroimaging method may be helpful for assessing treatment response and tumor progression. 

Tom Peeters¹, Vincent Breukels¹, Krissie Lenting², Sanne van Lith², Arno van Rooij³, Remco Molenaar⁴, William Leenders², and Arend Heerschap^1
1Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, Netherlands, ²Pathology, Radboud university medical center, Nijmegen, Netherlands, ³Laboratory Medicine, Radboud university medical center, Nijmegen, Netherlands, ⁴Cell Biology and Histology, Academic Medical Center, Amsterdam, Netherlands

This study demonstrates that in IDH1-mutant tumor cells the pool of oncometabolite 2HG is predominantly replenished by αKG precursors glutamine and glutamate, and to a lesser extent by glucose-derived metabolites. Furthermore, we show that 2HG production is not significantly decreased when total the pool of glutamine and glutamate drops, which occurs upon substitution of glutamine by glutamate in the culture medium.

Elizabeth Maher¹, Kumar Pichumani², Venetia Sarode³, Tomoyuki Mashimo¹, Manoj Cheriyan¹, Vamsidhara Vemireddy¹, Barbara Haley¹, Dean Sherry², Roshni Rao⁴, Craig Malloy², and Robert Bachoo^5
1Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ³Pathology, UT Southwestern Medical Center, Dallas, TX, United States, ⁴Surgery, UT Southwestern Medical Center, Dallas, TX, United States, ⁵Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, United States

Metabolic reprogramming of bioenergetic substrate utilization was shown in primary and metastatic brain tumors.  Whether the use of substrates other than glucose to fuel the citric acid cycle is a property of cancer cell growth in the brain or a fundamental property of a transformed cell is not known.  To address this question we studied early stage breast cancer patients using infusion of ¹³C-glucose or ¹³C-acetate during initial surgery.  ¹³C-NMR spectra of resected tumors show that acetate but not glucose is oxidized in the citric acid cycle, suggesting that acetate may contribute to energy production in these early stage cancers.

Silvia Rizzitelli¹, Stefan Glöggler¹, Noël Pinaud¹, Gerard Raffard¹, Veronique Bouchaud¹, Vanessa Zhendre¹, Stephane Sanchez¹, Alan Wong², and Yannick Cremillieux^1
1Centre de Resonance Magnétique des Systemes Biologiques, University of Bordeaux, Bordeaux, France, ²NIMBE/LSDRM, CEA-Saclay, Gif-sur-Yvette, France

The challenge of this study was to investigate the ability of a custom-made 1H microsolenoidal coil operating at 7T, with an inner volume of 1 μL, of visualizing the on-line metabolism of brain metabolites through the use of a microdialysis catheter, carried out with the complementarity of MRI and MRS techniques. ¹H-MR spectra of in vitro (human gliobastoma cells) and in vivo (healthy and glioblastoma-bearing rats) were acquired every 3.50 minutes to monitor the real-time variations of metabolites concentration, after injection of ¹³C labelled compunds. 

Menglin Cheng¹, Asif Rizwan¹, Zaver M. Bhujwalla^1,2, Lu Jiang¹, and Kristine Glunde^1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

This study shows that the widely used chemotherapeutic drug doxorubicin increases the ¹H or ³¹P MRS detectable glycerophosphocholine (GPC) concentration, while decreasing the phosphocholine (PC) concentration in human MCF-7 and MDA-MB-231 breast cancer cell lines. This GPC increase and PC decrease was caused by doxorubicin-induced decreases in the expression of the GPC-phosphodiesterase GDPD6, choline kinase α, and phospholipase D1. GDPD6 silencing was able to counteract the doxorubicin-induced promotion of breast cancer cell migration, which can occur at low doxorubicin concentrations. GPC, PC, and PC/GPC may serve as non-invasive surrogate makers of therapeutic response in breast cancer patients undergoing doxorubicin chemotherapy. 

Sami Alghamdi^1,2, Gary Cowin¹, Ian Brereton¹, and Yasvir Tesiram^1
1Centre for Advanced Imaging, University of Queensland, Brisbane, Australia, ²Dept. of Radiological sciences,King Saud University, Riyadh, Saudi Arabia

To investigate the correlation between fat fraction (FF) measured by in/out-phase (IP/OP) imaging, with transverse relaxation time (mono- and bi-exponential T2 values) and their relationship with nodular and tumour formation in the liver of rats maintained on a choline and amino acid modified diet (CDAA diet).

María Jiménez-González¹, Sandra Plaza-García¹, Géraldine Pastor¹, and Torsten Reese^1
1Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Spain

We developed a pancreatic tumor xenograft model in a nude mice to study characteristics of nearby lymph nodes. Using non invasive in vivo MR imaging at 11.7 Tesla, we monitored the tumor progression from 8 to 20 weeks. We observed enlarged lymph nodes in tumor bearing animals comparing to controls. Histological analysis  demonstrated the presence of significant histiocytosis but not metastasis. Our study suggests that lymph node histiocytosis, in absence of functional adaptative immune system, plays a significant role of the innate immuno defense against cancer cells spreading.