Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy

Tumor Therapy Response: Preclinical & Clinical

Thursday 15 May 2014
Blue 1 & 2  16:00 - 18:00 Moderators: Arvind Pathak, Ph.D., Natalie J. Serkova, Ph.D.

16:00 0912.   Effect of pantethine on ovarian tumor progression and choline metabolism
Marie-France Penet1, Delia Mezzanzanica2, Franca Podo3, Max de Reggi4, Bouchra Gharib4, and Zaver M. Bhujwalla1
1JHU ICMIC Program, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy,3Department of Cell Biology and Neurosciences, Section of Molecular and Cellular Imaging, Istituto Superiore di Sanità, Rome, Italy, 4Neurobiology of Cellular Interactions and Neuropathophysiology, UMR CNRS 7259, Aix-Marseille University, Marseille, France

Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here we have assessed the effect of pantethine on tumor growth and metabolism using MRI and high resolution MRS, respectively, in an orthotopic model of ovarian cancer. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence.

16:12 0913.   Acquired resistance to sunitinib is not associated with rescue angiogenesis in 786-O renal cell carcinoma xenografts - permission withheld
Simon P Robinson1, Naveen S Vasudev2, and Andrew R Reynolds2
1Division of Radiotherapy & Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom

The response of 786-O RCC xenografts to sunitinib was investigated using susceptibility contrast MRI with USPIO particles. Fractional blood volume (fBV) was significantly reduced after 2 weeks daily treatment in the absence of any change in tumour volume. This reduced fBV was maintained in 786-O xenografts exhibiting acquired resistance to sunitinib.

16:24 0914.   
Assessment of the response of colorectal tumours to imatinib mesylate therapy using carbogen and hypercapnia gas challenges
Miguel R. Goncalves1, Simon Walker-Samuel1, Rajiv Ramasawmy1,2, Sean P. Johnson2, R. Barbara Pedley2, and Mark F. Lythgoe1
1UCL Centre for Advanced Biomedical Imaging, Division of Medicine, London, United Kingdom, 2UCL Cancer Institute, London, United Kingdom

We present the results of a tumour therapy study with the antiangiogenic agent imatinib mesylate, which was assessed using gradient-echo MRI alongside hyperoxia and hypercapnia challenges. Median carbogen-ΔR2*, carbogen-ΔR1 and hypercapnia-ΔGRE-SI did not change with therapy. However, significant changes in the spatial heterogeneity of carbogen-ΔR2* and hypercapnia-ΔSI were observed. These results are possibly due to the combined effect of a number of localised phenomena, given the heterogeneous nature of the tumour vasculature.

16:36 0915.   
Imaging biomarkers of cell death: a comparison between viscoelasticity and ADC in an orthotopic breast cancer xenograft model
Jin Li1, Yann Jamin1, Jessica K.R. Boult1, John C. Waterton2, Ralph Sinkus3, Michelle D. Garrett4, and Simon P. Robinson1
1Division of Radiotherapy & Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Personalised Healthcare and Biomarkers, AstraZeneca, Macclesfield, Cheshire, United Kingdom, 3BHF Centre of Excellence, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St Thomas' Hospital, London, United Kingdom, 4Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Comparison of MRE-derived imaging biomarkers of viscoelasticity (|G*|) and ADC in orthotopically propagated BT474 breast cancer xenografts revealed a close spatial association and quantitative correlation of reduced |G*| and elevated ADC with pathologically-confirmed cell death. A stronger and more significant correlation between |G*| and cell death supports |G*| as a potentially more sensitive biomarker of cell death than ADC.

16:48 0916.   MRI Evaluation of a Peptide-Coated Nanoparticle as a Potential Therapy Against Preclinical Brain Metastatic Breast Cancer
Amanda M Hamilton1, Sallouha Aidoudi-Ahmed2, Venkata R Kotamraju2, Shweta Sharma2, Paula J Foster1, Kazuki N Sugahara2, Erkki Ruoslahti2, and Brian K Rutt3
1Robarts Research Institute, London, Ontario, Canada, 2Sanford-Burnham Medical Research Institute, California, United States, 3Stanford University, California, United States

MRI was used to evaluate the treatment efficacy of iRGD-NW, a magnetic nanoparticle coated with a tumor-penetrating peptide in a preclinical breast cancer brain metastasis model. Mice received saline, iRGD-NW (tumor-homing) or CRGDC-NW at day (td) 6 or 12 post-cell injection. Tumor formation was evaluated by MRI at two time points after treatment administration. Td6 iRGD-NW mice displayed significantly lower tumor burden and signal void retention than that of saline mice. There was no observed treatment effect for td12 mice. Results showed that iRGD-NW had a significant time-dependent effect on tumor burden and suggest a potential use in metastasis prevention.

17:00 0917.   Early therapy evaluation of sunitinib for gastrointestinal stromal tumors using quantitative perfusion and diffusion weighted magnetic resonance imaging: a pilot study
Hyunki Kim1, Desiree Morgan1, David Sarver2, Kyle Lee1, T. Beasley1, and James Posey1
1University of Alabama at Birmingham, Birmingham, AL, United States, 2University of Arkansas for Medical Sciences, AR, United States

Quantitative DCE-MRI and DWI were successfully utilized in GIST patients to measure the perfusion and diffusion parameters of tumors. Significant decreases of Ktrans and kep values were observed in GISTs after sunitinib therapy, while tumor ADC values were significantly increased likely reflecting favorable anti-tumor effects. Tumor Ktrans change was significantly correlated with tumor-volume change, and therefore it may serve as an effective surrogate biomarker, especially when applied at earlier time points, to assess the therapeutic efficacy of sunitinib.

17:12 0918.   Evidence for Caution in DCE-MRI Assessment of Response to Antiangiogenic Therapy Using the Reference Tissue Method
Wei Huang1, Aneela Afzal1, Megan L Holtorf1, and Christopher W Ryan1
1Oregon Health & Science University, Portland, Oregon, United States

DCE-MRI studies were performed on eight soft-tissue sarcoma patients to assess responses to treatment regimen of antiangiogenic agent plus conventinal chemoradiotherapy. Significant Ktrans and kep decreases were found in normal muscle regions adjacent to the tumor following initial 2 weeks of antiangiogenic therapy only. The results suggest that caution must be taken in DCE-MRI evaluation of response to antiangiogenic treatment using the reference tissue method.

17:24 0919.   
Multiparametric MRI detection and prediction of response to neoadjuvant chemotherapy in breast cancer.
Elizabeth AM O'Flynn1, David Collins2, James D'Arcy2, Maria Schmidt2, Kabir Mohammed3, and Nandita M deSouza1
1Clinical Magnetic Resonance, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom, 2Clinical Magnetic Resonance, Insitute of Cancer Research, Sutton, Surrey, United Kingdom, 3Statistics, Royal Marsden Hospital, Sutton, Surrey, United Kingdom

We investigate the role of multiparametric MRI in the prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer. 27 women underwent breast MRI at 3T prior to and after two cycles of NAC. Values for ADC, R2*, Ktrans, ve, kep and IAUGC were recorded pixel-by-pixel. The enhancement fraction (EF) was calculated for each patient. The percentage decrease in EF after 2 cycles was the best predictor of complete pathological response on discriminant analysis. EF should be considered as a potential biomarker for predicting response to NAC.

17:36 0920.   Quantitative DCE-MRI Assessment of Breast Cancer Response to Neoadjuvant Chemotherapy
Alina Tudorica1, Karen Y Oh1, Stephen Y-C Chui1, Nicole Roy1, Megan L Troxell1, Yiyi Chen1, Arpana Naik1, Megan L Holtorf1, Aneela Afzal1, Zunqiu Chen1, Charles S Springer1, Xin Li1, and Wei Huang1
1Oregon Health & Science University, Portland, Oregon, United States

Fifteen women with breast cancer underwent DCE-MRI before, during, and after neoadjuvant chemotherapy. Pharmacokinetic analysis of DCE-MRI data were performed using Standard (Tofts) model (SM) and Shutter-Speed model (SSM). After only one cycle of therapy, % changes in SM and SSM Ktrans and kep, and SSM-unique Tau_i, as well as absolute values of Ktrans and kep, provieded excellent early predictions of pathologic complete response. Following therapy completion, tumor Tau_i was inversely, while Ktrans and tumor size were positively, correlated with residual disease burden. In conclusion, DCE-MRI functional parameters provided earlier prediction of response and more accurate assessment of residual disease compared to tumor size measurement.

17:48 0921.   Variations in DCE-MRI Assessment of Breast Cancer Therapy Response: A Multicenter Data Analysis Challenge
Wei Huang1, Xin Li1, Xia Li2, Ming-Ching Chang3, Matthew J Oborski4, Dariya I Malyarenko5, Mark Muzi6, Guido H Jajamovich7, Andriy Fedorov8, Yiyi Chen1, Alina Tudorica1, Sandeep N Gupta3, Charles M Laymon4, Kenneth I Marro6, Hadrien A Dyvorne7, James V Miller3, Thomas L Chenevert5, Thomas E Yankeelov2, James M Mountz4, Paul E Kinahan6, Ron Kikinis8, Bachir Taouli7, Fiona Fennessy8, and Jayashree Kalpathy-Cramer9
1Oregon Health & Science University, Portland, Oregon, United States, 2Vanderbilt University, Nashville, Tennessee, United States, 3General Electric Global Research, Niskayuna, New York, United States, 4University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 5University of Michigan, Ann Arbor, Michigan, United States, 6University of Washington, Seattle, Washington, United States, 7Icahn School of Medicine at Mount Sinai, New York, New York, United States, 8Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States, 9Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States

Seven institutions of the NCI-sponsored Quantitative Imaging Network (QIN) participated in a DCE-MRI data analysis challenge, in which 12 pharmacokinetic models/algorithms (including Tofts model, extended Tofts model, and Shutter-Speed model) were used to analyze shared breast DCE-MRI data collected at one center before and after one cycle of neoadjuvant chemotherapy, from 10 breast cancer patients. Tumor ROI definition, AIF, and precontrast T1 were fixed for analysis of each data set across all algorithms. Considerable variations in DCE-MRI parameters were found among the algoritms with Ktrans wCV as high as 0.59. Encouragingly, Ktrans and kep values after one therapy cyles and their % changes (relative to baselin) obtained from all algorithms provided good to excellent early prediction of pathologic response.