Gilberto S. Almeida¹, Philippa King², Yann Jamin¹, Albert Hallsworth², Hannah Webber², Sergey Popov³, Louis Chesler², and Simon P. Robinson^1
1Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²Clinical Studies, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, ³Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Both Vascular Endothelial Growth Factor (VEGF) and the Hepatocyte Growth Factor (HGF)/c-MET signalling pathway are implicated in the progression of human neuroblastoma. In this study we demonstrate the efficacy of cabozantinib, a small-molecule kinase inhibitor active against both VEGFR2 and MET and currently in clinical trials against neuroblastoma, in the Th-MYCN genetically engineered mouse model of neuroblastoma and established both native spin lattice relaxation time T1 and transverse relaxation rate R2* as early non-invasive biomarkers of response, which were associated with significant increase in necrosis, and significant decrease in microvessel density.

Deborah K. Hill^1,2, Eugene Kim^1,2, Jose R. Teruel^1,2, Siver A. Moestue^1,2, and Tone F. Bathen^1
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Sør Trøndelag, Norway, ²St. Olavs University Hospital, Trondheim, Sør Trøndelag, Norway

The effectiveness of DW-MRI for both detecting early onset of prostate cancer (PCa) and for characterising disease progression was investigated for the transgenic adenocarcinoma of the mouse prostate (TRAMP) model in mice. DWI facilitated early detection of tumour onset in TRAMP mice prostates before lesions were seen on high-resolution T2W images. Histograms are sensitive to distinguishing cancer from prostate tissue, where bimodal distributions were clearly visible in the case of cancer onset. Median ADC values of prostate regions were in agreement with literature values for different stages of PCa progression, thus providing a non-invasive means to assess cancer aggressiveness.

Samata M Kakkad^1,2, Jiangyang Zhang¹, Alireza Akhbardeh¹, Desmond Jacob¹, Meiyappan Solaiyappan¹, Michael A Jacobs¹, Venu Raman¹, Dieter Leibfritz², Kristine Glunde¹, and Zaver M Bhujwalla^1
1Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²University of Bremen, Bremen, Germany

Col1 fibers play an important role in molecular transport and cancer cell dissemination. We investigated the influence of Col1 fibers on water diffusion, using a breast cancer xenograft fluorescing under hypoxia. We observed that hypoxic regions contained significantly fewer Col1 fibers, and were characterized by a lower ADC and FA compared to normoxic tumor regions. In vivo DTI distribution patterns were spatially similar to those observed ex vivo, suggesting that noninvasive DTI parameters provided noninvasive indices of Col1 fiber distribution in tumors.

Paula Foster^1,2, Amanda Hamilton¹, and Carmen Simedrea^1
1Imaging, Robarts Research Institute, London, Ontario, Canada, ²Medical Biophysics, Western University, London, Ontario, Canada

MRI was used to track growth of brain metastases and dormant (non proliferative) cancer cells in a mouse model of concomitant tumor resistance. Our major result was that the presence of a primary mammary fat pad tumor limited the development of secondary metastases in the brain.

J C Montejano¹, K M Huber¹, V F Borges¹, P J Schedin², and N J Serkova^1
1University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States, ²Oregon Health and Science University, Oregon, United States

In this study, superparamagnetic iron nanoparticles (SPION) were used as a contrast agent for the imaging of macrophage driven inflammation in postpartum pregnancy associated breast cancer (PPABC) by T2-MRI. A cohort of immunocompetent BALB/C mice were injected with a murine breast cancer cell line and injected with SPION contrast 24 hours prior to imaging. When compared to virgin counterparts, postpartum mice showed a large decrease in T2 relaxation times. This study has shown that SPIONs are an appropriate contrast agent for the assessment of the TAM-rich tumor microenvironment in PPABC.

Jinjin Zhang¹, Alicia A. Petryk², Russell Reeves³, Djaudat Idiyatullin¹, Hattie L. Ring^1,4, P. Jack Hoopes^2,3, and Michael Garwood^1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ²Thayer School of Engineering, Dartmouth College, NH, United States, ³Geisel School of Medicine, Dartmouth College, NH, United States, ⁴Department of Chemistry, University of Minnesota, MN, United States

The ability to accurately and sensitively image tumor iron oxide nanoparticles (IONPs) is essential for their use as a therapeutic modality in clinical cancer medicine. In this study, the quantification of IONPs in a murine breast tumor model at high, but clinically relevant, concentrations was done by using positive contrast from SWIFT sequence. IONPs were administered by intra-tumoral (IT) or intravenous (IV) injection. Polyethylene glycol (PEG) and low dose radiation enhanced IONP tumor uptake. The T1 maps measured by the SWIFT sequence provided quantitative and qualitative estimations of IONP at concentrations significantly higher (x30) than previously reported.

Marie Anne Richard¹, Vincent Turgeon¹, Jérémie P. Fouquet¹, Luc Tremblay¹, Réjean Lebel¹, and Martin Lepage^1
1Centre d’imagerie moléculaire de Sherbrooke (CIMS), Université de Sherbrooke, Sherbrooke, Québec, Canada

Signal in PET imaging is modulated by the perfusion and metabolism of the radiotracer. It would be possible to decouple these parameters through combined PET-MRI using an unmetabolized MRI contrast agent with similar perfusion kinetics as the radiotracer. Sequential MRI and PET scans were performed in rats using Gd-DTPA and FDG. Pharmacokinetic parameters were extracted based on a two-tissue model and statistical analysis was performed to determine if perfusion and elimination are correlated between both probes. Preliminary results suggest that perfusion is correlated, whereas elimination is not.

Hyunki Kim¹, Yolanda Hartman¹, Guihua Zhai¹, Thomas Chung¹, Melissa Korb¹, Tong Zhou¹, and Eben Rosenthal^1
1University of Alabama at Birmingham, Birmingham, AL, United States

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) showed that tumor microvascular perfusion was significantly suppressed by anti-EMMPRIN antibody alone or in combination with X-radiation or cisplatin in head and neck cancer mouse models. The early change of tumor perfusion parameters following anti-EMMPRIN therapy with/without cisplatin was significantly correlated with the tumor volume change, proliferation cell density, and microvessel density, but not when X-radiation treated group was included. Therefore DCE-MRI may be used to predict the therapeutic efficacy of anti-EMMPRIN antibody with/without cisplatin, but not with X-radiation.

Zhongwei Zhang¹, Qing Yuan¹, Heling Zhou¹, and Ralph P Mason^1
1Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States

Few studies have been performed to reveal the changes of tumor microenvironment such as diffusion and perfusion parameters in response to oxygen challenge. The purpose of this study was to evaluate the effect of oxygen challenge on tumor heterogeneity, diffusion and perfusion parameters at the microscopic level. The current study demonstrated that IVIM diffusion MRI provided powerful insight into tumor perfusion. On the other hand, diffusion stretched-exponential model was sensitive to the changes of tumor heterogeneity, Combining these two models may serve as potential biomarker to evaluate tumor responses to oxygen.

Brittany Dashevsky¹, Krishna Juluru^1,2, Timothy D'Alfonso¹, Elizabeth Sutton², Eric Aronowitz¹, Ashley E. Giambrone¹, and Doug Ballon^1
1Weill Cornell Medical College, New York, NY, United States, ²Memorial Sloan Kettering Cancer Center, New York, NY, United States

With 7T MR imaging of ex vivo fresh unfixed breast and lymph specimens at a spatial resolution of 60 x 60 x 90µm, we identified characteristic features of both benign and malignant lesions compared with a light microscopy standard. Ultra-high resolution MRI offers a new tool in the management of breast cancer in ways that include defining pathology, delineating tumor margins, and optimizing specimens for pathologic processing. This tool promotes a novel approach to radiology - pathology collaboration and demonstrates the capabilities of 7T MR.