Georgios Batsios¹, Meryssa Tran¹, Celine Taglang¹, Anne Marie Gillespie¹, 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

Metabolic reprogramming is a fundamental hallmark of cancer, which can be exploited for non-invasive tumor imaging. Deuterium magnetic resonance spectroscopy (²H-MRS) recently emerged as a novel, clinically applicable method of non-invasively monitoring flux from ²H-labeled substrates to metabolic products. However, to date, preclinical studies have been performed in vivo, an endeavor that suffers from low-throughput and potential waste of animal lives, especially in treatment response studies. Here, we demonstrate the ability to quantify metabolism of ²H-MRS probes in live cell suspensions. Our studies will expedite the identification of novel ²H-MRS probes for imaging brain tumors and potentially other cancers.

James D Barnett¹, Marie-France Penet^1,2, Raj Kumar Sharma¹, Balaji Krishnamachary¹, Yelena Mironchik¹, and Zaver Bhujwalla^1,2,3
1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Our findings demonstrate that tumors drive metabolic alterations in the spleen. These metabolic changes may contribute to immune suppression and poor prognosis.

Adam Philip Gaunt¹, Jennifer Lewis¹, Friederike Hesse¹, Irene Marco-Rius¹, Kevin Brindle¹, and Arnaud Comment^1,2
1University of Cambridge, Cambridge, United Kingdom, ²General Electric Healthcare, Chalfont St Giles, United Kingdom

A hyperpolarised [1-¹³C]lactate solution prepared by dynamic nuclear polarization at 7T and 1.4K using photo-irradiated alpha-ketoglutarate as the polarizing agent was injected at low dose in healthy rodents to allow measuring in vivo metabolism in the rodent brain and liver at physiological concentration. As a result of the large ¹³C polarisation, it was possible to detect metabolic products of [1-¹³C]lactate in vivo, including [1-¹³C]pyruvate and ¹³C-bicarbonate. The observed pyruvate-to-lactate ratios were commensurate with in vitro values previously reported in the literature. The purely endogenous composition of the solution offers the possibility of performing similar measurements in humans.

Hassan Bagher-Ebadian¹, Stephen Brown¹, Olivia Valadie¹, Julian A Rey², Malisa Sarntinoranont², James R Ewing³, and Indrin J Chetty^1
1Radiation Oncology, Henry Ford Cancer Institute, Detroit, MI, United States, ²Department of Mechanical & Aerospace Engineering, University of Florida, Gainesville, FL, United States, ³Neurology, Henry Ford Cancer Institute, Detroit, MI, United States

Wavelet-analysis of DCE-MR images was performed to explore the association between radiomics information and relaxivity-change (ΔR₁) in human U251n tumors grown in rat brains. Sixteen DCE-MRI experiments (8 rats before- and after- radiation) were studied. Wavelet-decomposition analysis was performed using ΔR₁ time trace. Frequency-based localized approximations of ΔR₁ with four degrees of regularities were estimated and compared to the volume-transfer-constant (K^trans, calculated from a modified Tofts-model pharmacokinetic analysis). Results confirm strong associations between wavelet-based radiomic information and contrast uptake/flow/leakage in the tumor vasculature. Results suggest that radiomics has potential as a biomarker of tumor physiology.

Jessica K.R. Boult¹, Upasana Roy¹, Carolina Bernauer², Carol Box¹, Louise Howell³, Elise Y. Lepicard¹, Yann Jamin¹, James P.B. O'Connor¹, Janet M. Shipley², and Simon P. Robinson^1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom, ²Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom, ³Core Research Facilities, The Institute of Cancer Research, London, United Kingdom

Hypoxic gene signatures are prevalent in paediatric rhabdomyosarcomas and are important in conferring resistance to standard treatments. Oxygen-enhanced MRI (OE-MRI) and histological assessment of pimonidazole adduct formation show that xenografts derived from three human rhabdomyosarcoma cell lines exhibit high levels of hypoxia with differences in vascular perfusion evident between the models.

There is much interest in hypoxia-alleviating strategies to reduce tumour hypoxia for therapeutic gain, and these will be assessed in rhabdomyosarcoma models in vivo using OE-MRI. A reduction in hypoxia in response to atovaquone in spheroids derived from the same rhabdomyosarcoma cell lines in vitro has been confirmed.
 

Sudath Hapuarachchige^1,2, Ge Si^1,3, Catherine Foss¹, Cyril Barinka⁴, and Dmitri Artemov^1,2
1Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, MD, United States, ²Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States, ³Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, United States, ⁴Laboratory of Structural Biology, Institute of Biotechnology of the Czech Academy of Sciences, Vestec, Czech Republic

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancers (PC) compared to normal tissues. Hence, PSMA can be used as a diagnostic biomarker and biological target to deliver drugs in PC therapy. In this study, we have conjugated ultra-small superparamagnetic iron oxide nanoparticles with mertansine (DM1), a chemotherapeutic drug, novel anti-PSMA 5D3 antibody, and NIR CF-750 fluorophore. This multimodality image-guided drug delivery system was evaluated in PC mouse models using in vivo fluorescent imaging and MRI at 9.4T. Promising results encourage further development of targeted image-guided drug delivery platforms for PC therapy.

Li Liu¹, Donghan Yang¹, Janaka Wansapura¹, Guiyang Hao¹, Ralph P. Mason¹, and Li Zhang^2
1Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Biological Sciences, University of Texas at Dallas, Richardson, TX, United States

The goal was to evaluate the activity of two novel heme targeting drugs in Non-Small Cell Lung Cancer models using multi-modality imaging. We found that the novel heme targeting drugs CycT (cyclopamine tartrate) and HSP2 (heme-sequestering peptide 2) were effective in suppressing NSCLC lung tumor growth as assessed by multimodality imaging and confirmed by pathology/histology. MRI detected the H1395 and H1299 orthotopic xenografts and was correlated with PET studies and histology.