Room 355 EF

13:30 - 15:30

Moderators:

Nandita M. DeSouza, Tom W. J. Scheenen

Timothy James Graham¹, Gary Box², Ruth Riisnaes², Susana Miranda², Gerhardt Attard², Johann S. de Bono², Suzanne A. Eccles², Faith E. Davies², and Simon P. Robinson^1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

With the development of more targeted therapeutics to treat malignant bone disease has come the associated challenge of developing more clinically relevant pre-clinical models, and identifying new non-invasive techniques capable of assessing the tumour phenotype and treatment response. To this end, a mouse model of castrate-resistant, prostate bone metastasis, propagated by direct intraosseous injection of cells, and its response to cabozantinib, has been investigated by quantitative imaging methods.

Jana Cebulla¹, Siver A. Moestue¹, Else Marie Huuse¹, Geir Bjørkøy², Tone Frost Bathen¹, and Ingrid Susann Gribbestad^1
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, ²Department of Technology, University College of Sør-Trøndelag (HiST), Trondheim, Norway

The PI3-Kinase pathway is often upregulated in cancer cells and is therefore a promising target for anticancer therapy. This novel treatment strategy induces a need for biomarkers that can non-invasively and repeatedly assess therapy response. In this study we used diffusion weighted MRI to evaluate changes in the apparent diffusion coefficient (ADC) caused by PI3-kinase/mTOR inhibition in ovarian tumor xenografts. For responding tumors we found a significant increase in median ADC values and a decrease in kurtosis and skewness of ADC histograms, suggesting that these parameters are promising candidates for clinical biomarkers for PI3-Kinase/mTOR inhibition.

Yunzhou Shi¹, Jason Oeh², Jeffrey Eastham-Anderson³, Sharon Yee², David Finkle², Franklin V. Peale³, Jed Ross¹, Maj Hedehus¹, Nicholas van Bruggen¹, Rayna Venook², Sarajane Ross², Deepak Sampath², and Richard A. D. Carano^4
1Biomedical Imaging, Genentech Inc.(Roche Group), South San Francisco, CA, United States, ²Translational Oncology, Genentech Inc.(Roche Group), South San Francisco, CA, United States,³Pathology, Genentech Inc.(Roche Group), South San Francisco, CA, United States, ⁴Biomedical Imaging, Genentech, South San Francisco, CA, United States

The effect of a novel dual PI3K/mTOR inhibitor on tumor oxygen level was studied using a novel approach that combines ¹⁹F-MRI T₁ mapping with diffusion-based multispectral K-means clustering. The current study aims to elucidate the role of PI3K/mTOR signaling on oxygen level in viable tumor. An anti-angiogenic agent, B20.4.1.1, was employed as a positive control for its known anti-vascular effects. We were able to monitor pO₂ for 72h without fluorine signal loss. The current results advocate for the use of the multispectral ¹⁹F-MRI technique as a tool to better understand the mode of action of therapies that alter tumor’s microenvironment.

Kimberly Brewer^1,2, Christa Davis³, Iulia Dude³, Genevieve Weir¹, Olivia Stanley³, Mohan Karkada¹, Marc Mansour¹, and Chris Bowen^2,3
1Immunovaccine Inc., Halifax, NS, Canada, ²Biomedical Engineering, Dalhousie University, Halifax, NS, Canada, ³Institute for Biodiagnostics (Atlantic), Halifax, NS, Canada

A growing area of interest in cancer research is the behaviour of regulatory cells such as myeloid derived suppressor cells and regulatory T cells. These cells suppress both inherent and induced immune responses (i.e. via treatments such as immunotherapies) resulting in the underperformance of many anti-cancer treatments. Our current work used MRI to investigate the migration patterns of three types of SPIO-labeled immune cells in a mouse tumor model. The objectives of this study were to demonstrate reliable homing of regulatory and effector cells to tumors and lymph nodes, and observe changes in these patterns in response to cancer immunotherapy.

Guang Jia¹, Huyen Thanh Nguyen¹, Kamal S. Pohar², Amir Mortazavi³, Zarine K. Shah¹, Lai Wei⁴, and Michael V. Knopp^1
1Department of Radiology, The Ohio State University, Columbus, OH, United States, ²Department of Urology, The Ohio State University, Columbus, OH, United States, ³Department of Medical Oncology, The Ohio State University, Columbus, OH, United States, ⁴Center for Biostatistics, The Ohio State University, Columbus, OH, United States

This study was conducted to evaluate the role of APT-MRI in bladder cancer neoadjuvant chemotherapy response assessment.

Alina Tudorica¹, Karen Y. Oh¹, Stephen Y.-C. Chui¹, Nicole Roy¹, Megan L. Troxell¹, Yiyi Chen¹, Arpana Naik¹, Ariel Lopez-Chavez¹, Megan L. Holtorf¹, Aneela Afzal¹, Mohan L. Jayatilake¹, Zunqiu Chen¹, Charles S. Springer, Jr.¹, Xin Li¹, and Wei Huang^1
1Oregon Health & Science University, Portland, OR, United States

Eleven consecutive women with locally advanced breast cancer underwent research DCE-MRI before, after one cycle, at midpoint, and after completion of neoadjuvant chemotherapy. MRI data were analyzed using the Standard and Shutter-Speed models (SM and SSM). % changes in tumor Ktrans (SM and SSM), kep (SM and SSM), and tau_i (SSM only), as well as the absolute values of Ktrans (SSM) and kep (SM and SSM) after one cycle of therapy completely discriminated 3 responders from 8 non-responders. The tau_i value after therapy correlated significantly with residual disease burden.

Marco Borri¹, Maria A. Schmidt¹, Ceri Powell², Dow-Mu Koh^1,3, Angela Riddell³, Kate Newbold², and Martin O. Leach^1
1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden, Sutton, Surrey, United Kingdom, ²Head and Neck Dept., The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ³Radiology Dept., The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom

One of the main challenges in the management of head and neck squamous cell carcinomas (HNSCC) is the inability to predict outcome because of tumour heterogeneity. We propose a method, based on cluster analysis, to robustly partition head and neck lesions in sub-regions using complementary functional information from DCE and DWI. This approach was able to spatially describe functional heterogeneity in a cohort of patients with histologically proven HNSCC undergoing radical chemoradiotherapy, and allowed identification of sub-regions of the tumours which were affected differently by treatment and their characterization with functional parameters.

Sean Peter Johnson ¹, Rajiv Ramasawmy², Adrienne E. Campbell-Washburn², Mathew Robson¹, Jack Wells², Vineeth Rajkumar¹, Simon Walker-Samuel², Mark F. Lythgoe², and Rosamund Barbara Pedley^1
1Cancer Institute, University College London, London, Greater London, United Kingdom, ²Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom

We present data comparing the ability of arterial spin labelling (ASL) perfusion measurements and R2* to assess response to vascular disrupting agent therapy in a mouse liver metastasis model. A significant increase in R2* (p<0.01, n=12) and a significant decrease in perfusion (p<0.01, n=18) were measured. Baseline perfusion was significantly correlated with the subsequent change in perfusion at 90 minutes following therapy, whilst baseline R2* values did not show a relationship with response. No significant correlation was found between perfusion and R2* post-therapy changes.

Yonggang Lu¹, Jacobus F.A. Jansen², Hilda E. Stambuk³, Gaorav Gupta⁴, Nancy Lee⁴, Mithat Gonen⁵, Andre E. Moreira⁶, Snehal G. Patel⁷, Joseph O. Deasy¹, Jatin P. Shah⁷, and Amita Shukla-Dave^1,3
1Medical Physics Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, ²Department of Radiology, Maastricht University, Maastricht, Netherlands, ³Radiology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, ⁴Radiation Oncology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States,⁵Biostatistics Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, ⁶Pathology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States,⁷Surgery Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States

The purpose of this study was to evaluate the efficacy of intravoxel incoherent motion imaging in predicting treatment outcome in patients with head and neck cancer. Sixteen patients with both primary tumor and metastatic nodes were enrolled. The results demonstrated that measures of std(D) in both primary tumors and metastatic nodes were found to be predictors of outcome (progression free (PFS) and overall survival (OS)), but std(D) from primary tumors had more sensitivity in predicting PFS than from metastatic nodes. After appropriate validation in larger patient population, these findings may be useful in optimizing treatment planning and improving patient care.

Matthew R. Orton¹, Christina Messiou², David John Collins¹, Veronica A. Morgan², Dionysis Papadatospastos³, Andre Brunetto³, Jooern Ang³, Helen Mann⁴, Jean Tessier⁴, Helen Young⁴, Stan Kaye³, Johann S. de Bono³, Martin O. Leach¹, and Nandita M. De Souza^1
1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²Radiology Department, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ³Department of Medicine, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ⁴AstraZeneca, Macclesfield, Cheshire, United Kingdom

Although DWI measures have previously been reported demonstrating changes with anti-angiogenic agents at 28 days, the response at 7 days has not been widely reported as it is assumed that DWI is insensitive to perfusion changes with an antiangiogenic agent in such a short time-frame. The purpose of this study was to assess changes in DWI derived measures at both 7 and 28 days for a cohort of patients treated with Cediranib. Significant cohort changes are seen at 7 days and these can be detected using a number of diffusion attenuation models, in particular with the stretched-exponential model.