ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Preclinical Cancer Imaging: Molecular & Traditional
Wednesday 24 April 2013
Room 355 EF  10:00 - 12:00 Moderators: Kristine Glunde, Sabrina M. Ronen

10:00 0439.   
Quantitative MRI Reporter Gene Imaging of the Recruitment of Ferritin Over-Expressing Fibroblasts to the Vascular Niche of Solid Tumors
Moriel Vandsburger1, Marina Radoul1, Yoseph Addadi1, Senzeni Mpofu1, Batya Cohen1, and Michal Neeman1
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.

10:12 0440.   
in vivo Monitoring of Tumor Response to Anti-Cancer Therapy Using MRI and a Novel Caspase-3 Activatable Gadolinium Contrast Agent for Imaging Apoptosis
Prachi Pandit1, Deju Ye1, Adam Shuhendler1, Jianghong Rao1,2, and Brian K. Rutt1
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.

10:24 0441.   Monitoring the Effects of Bicarbonate Treatment on Tumor Extracellular pH Using AcidoCEST MRI
Liu Qi Chen1, Christy M. Howison2, Justin J. Jeffery2, Ian F. Robey3, and Marty Pagel2
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.

10:36 0442.   Investigating the Role of Macromolecular Transport in the Formation of Malignant Ascites and Metastases
Marie-France Penet1, Zhihang Chen1, Arvind P. Pathak1, Dmitri Artemov1, and Zaver M. Bhujwalla2
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.

10:48 0443.   Tracking 4T1-PiPSCs Homing to Primary and Metastatic Tumor with MRI
Hong Li1,2, Jianjun Wang3, Qianqian Li3, Mengfan Yan4, Guojun Wu4, Yimin Shen2, Ewart Mark Haacke2, and Jiani Hu2
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.

11:00 0444.   
Tumor Blood Flux Quantification Using Flow Enhanced MRI and Comparison with Histology
Olivier Reynaud1, Franoise Geffroy1, and Luisa Ciobanu1
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.

11:12 0445.   Synthesis and Evaluation of CREKA-Tris(Gd-DOTA)3 for MR Molecular Imaging of Breast Cancer
Zhuxian Zhou1, Zhen Ye1, Xueming Wu1, and Zheng-Rong Lu1
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

11:24 0446.   
The Relationship Between Short and Long Diffusion Time ADC Values in Rat Brain Tumors
Alexander D. Cohen1, Peter S. LaViolette2, and Kathleen M. Schmainda1,2
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 materials 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.

11:36 0447.   
Imaging Glucose Uptake in a Preclinical Brain Tumor Model Using GlucoCEST -permission withheld
Kannie W.Y. Chan1,2, Guanshu Liu1,3, Bachchu Lal3,4, Jeff W.M. Bulte2,5, John Laterra3,6, Dmitri Artemov7,8, Michael T. McMahon1,3, and Peter C.M. van Zijl1,3
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.

11:48 0448.   
Noninvasive Investigation of the Viscoelastic Properties of Intracranial Tumours with Magnetic Resonance Elastography
Yann Jamin1, Jessica K.R. Boult1, Jin Li1, Craig Cummings1, Jeffrey C. Bamber1, Ralph Sinkus2, and Simon P. Robinson1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2INSERM U773, CRB3, Centre de Recherche Biomdicale 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.