Room 355 EF

10:00 - 12:00

Moderators:

Kristine Glunde, Sabrina M. Ronen

Moriel Vandsburger¹, Marina Radoul¹, Yoseph Addadi¹, Senzeni Mpofu¹, Batya Cohen¹, and Michal Neeman^1
1Weizmann Institute of Science, Rehovot, None, Israel

We used over-expression of ferritin heavy chain (FHC) as an MRI reporter gene in CV-1 fibroblasts. The recruitment of FHC over-expressing fibroblasts to ovarian cancer tumors was quantitatively examined using bi-exponential modeling in order to determine the cell fraction of FHC over-expressing cells within a mixed cell population. In addition, mapping of fractional blood volume revealed preferential recruitment of FHC over-expressing fibroblasts to the vascular niche of growing tumors.

Prachi Pandit¹, Deju Ye¹, Adam Shuhendler¹, Jianghong Rao^1,2, and Brian K. Rutt^1
1Radiology, Stanford University, Stanford, CA, United States, ²Chemistry, Stanford University, Stanford, CA, United States

Non-surgical cancer treatments rely on re-induction of apoptosis to enable tumor regression, and hence early, noninvasive detection of apoptotic enzymes, like caspase is invaluable for therapy response monitoring. We have developed a Gd-based caspase-activatable contrast agent that can self-assemble into nanoparticles and provide signal enhancement at apoptotic sites. This work presents the first in vivo results in a doxorubicin-treated mouse model of cancer, which show significant difference in enhancement in the same tumor before and after treatment. We believe that the improved sensitivity and specificity achieved with our agent will make MRI even more attractive for cancer theranostics.

Liu Qi Chen¹, Christy M. Howison², Justin J. Jeffery², Ian F. Robey³, and Marty Pagel^2
1Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, ²Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ³University of Arizona Cancer Center, University of Arizona, Tucson, AZ, United States

We have developed a non-invasive MRI method that can accurately measure pHe to assess tumor acidosis, termed “acidoCEST MRI�. This method measures a ratio of the Chemical Exchange Saturation Transfer (CEST) effects of Iopromide (Ultravist®), a FDA approved contrast agent for X-ray/CT. We have applied acidoCEST MRI to monitor the effects of bicarbonate treatment on tumors of mammary carcinoma. Our method has strong clinical translation potential because it uses low saturation powers, incomplete saturation, and a clinically approved contrast agent.

Marie-France Penet¹, Zhihang Chen¹, Arvind P. Pathak¹, Dmitri Artemov¹, and Zaver M. Bhujwalla^2
1JHU ICMIC Program Division of Cancer Imaging Research The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²JHU ICMIC Program Division of Cancer Imaging Research The Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

Malignant ascites and metastatic spread of cancer are major causes of morbidity and mortality in prostate and ovarian cancer patients. Here we combined in vivo MRI and optical imaging to characterize the relationship between tumor vasculature, interstitial fluid transport, malignant ascites formation and metastases. We quantified the transport dynamics of the macromolecular contrast agent albumin-GdDTPA labeled with rhodamine in the tumor and in malignant ascites. Orthotopic, human prostate and ovarian tumor models, that frequently result in metastases and malignant ascites, are being used to better understand metastatic dissemination and malignant ascites formation and to develop new therapeutic strategies.

Hong Li^1,2, Jianjun Wang³, Qianqian Li³, Mengfan Yan⁴, Guojun Wu⁴, Yimin Shen², Ewart Mark Haacke², and Jiani Hu^2
1Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, ²Radiology, Wayne State University, Detroit, MI, United States,³Biochemistry and Molecular Biology, Wayne State University, Detroit, MI, United States, ⁴Pharmacology, Karmanos Cancer Institute,Wayne State University School of Medicine, Detroit, MI, United States

Stem cell-based cell-converting therapy is considered to be a future therapeutic strategy for cancer. In order to efficiently deliver cell-converting cancer therapy in a clinical setting, there is a need for a non-invasive imaging technique that confirms the successful targeted delivery of therapeutics. QQ-ferritin was prepared for labeling 4T1- protein-induced pluripotent stem cells (piPSCs) and effects of the labeling on cell viability were examined. A subcutaneous model was used to evaluate the sensitivity of in vivo MRI detection and a metastatic 4T1 model was used to study the feasibility of MRI tracking 4T1-piPSCs homing to primary and metastatic tumors. Major findings of this study are: 1) the QQ technique can label cells with virtually ¡°toxicity-free¡± ferritin for MRI cell-tracking, 2) QQ-labeled ferritin does not affect cell viability, 3) 4T1-piPSCs can home to both primary and metastatic tumors and 4) ferritin-labeled 4T1-piPSC offers high sensitivity for MRI detection.

Olivier Reynaud¹, Françoise Geffroy¹, and Luisa Ciobanu^1
1NeuroSpin, Saclay, France

Quantitative microvascular blood flux maps obtained at different developmental stages of the 9L rat brain tumor model using the magnetization transfer free FENSI technique highlight distinct flux patterns and vascular properties. Late stage measurements highlight a significant decrease of CBFlux inside the gliosarcoma (-40 %, consistent with previous CBF studies) and tumor compartmentalization (p < 0.05). The hyper- and hypo-perfused tumor regions revealed with FENSI correlate linearly with regions of high and low blood vessel concentration (R²=0.4) and microvascular area (R²=0.7) revealed with immunohistochemistry.

Zhuxian Zhou¹, Zhen Ye¹, Xueming Wu¹, and Zheng-Rong Lu^1
1Biomedical Engineering, Case Western Reserve Universtiy, Cleveland, OH, United States

MRI is a powerful medical imaging modality to display anatomical structures of body, especially useful for the detection and characterization of diseased soft tissues such as solid tumors. Various targeted contrast agents have been prepared for cancer molecular imaging with MRI. However, MRI is not effective for molecular imaging because of its low sensitivity. Most of these agents could not generate sufficient contrast enhancement because of low concentration of biomarkers on cancer cell surface. CREKA is a tumor-homing pentapeptide (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibronectin associated plasma protein clots in tumor stroma. Thus, we synthesized and evaluated a new tumor-targeted contrast agent CREKA-Tris(Gd-DOTA)3 for MR molecular imaging of breast cancer

Alexander D. Cohen¹, Peter S. LaViolette², and Kathleen M. Schmainda^1,2
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²Radiology, Medical College of Wisconsin, Milwaukee, WI, United States

Advanced imaging techniques, such as diffusion weighted imaging, have been developed to detect brain tumor progression and invasion. Biological systems are heterogeneous and contain physical boundaries that can hinder the motion of water molecules and lead to an underestimation of a material’s true diffusion coefficient when the diffusion time is large. This study looks at the relationship between short and long diffusion time apparent diffusion coefficient (ADC) values in a rat brain cancer model. The ADC difference between short and long diffusion time scans was significantly higher in tumor vs. normal cortex and correlated with the intravoxel heterogeneity index.

Kannie W.Y. Chan^1,2, Guanshu Liu^1,3, Bachchu Lal^3,4, Jeff W.M. Bulte^2,5, John Laterra^3,6, Dmitri Artemov^7,8, Michael T. McMahon^1,3, and Peter C.M. van Zijl^1,3
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States,⁴Department of Neurology, Kennedy Krieger Institute, Baltimore, MD, United States, ⁵Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ⁶Department of Neuroscience, Kennedy Krieger Institute, Baltimore, MD, United States, ⁷JHU In Vivo Cellular Molecular Imaging Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁸Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Neuroimaging has an important role in the diagnosis of tumors, especially to identify different stages of tumor development, the likelihood of metastasis, and the effects of treatment. Recently, Chemical Exchange Saturation Transfer (CEST) MR imaging of natural D-glucose (glucoCEST) was proposed as a novel molecular imaging approach with a biodegradable substrate for tumors. Here we apply this method to visualize glucose uptake in brain tumors, using an orthotopically implanted human brain tumor xenograft in mice. The results show that, using glucoCEST, the tumor glucose uptake can be clearly distinguished from brain glucose uptake.

Yann Jamin¹, Jessica K.R. Boult¹, Jin Li¹, Craig Cummings¹, Jeffrey C. Bamber¹, Ralph Sinkus², and Simon P. Robinson^1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, ²INSERM U773, CRB3, Centre de Recherche Biomédicale Bichat-Beaujon, Paris, France

Increased tissue rigidity is associated with a more invasive tumour phenotype. Non-invasive imaging biomarkers of mechanical properties of tumours can improve the diagnosis and staging of malignancies, and facilitate and accelerate the development of novel anti-cancer therapeutics. Innovative techniques such as magnetic resonance elastography (MRE) afford non-invasive biomarkers of the mechanical or visco-elastic properties of tissue in vivo. The visco-elastic properties of U87, RG2 and MDA-MB-231 tumours propagated intracranially in mouse brain were quantified using MRE, and interestingly revealed that all three tumours were softer than residual brain.