New Agents, New Targets
Click on to view the abstract pdf. Click on to view the recorded presentation.
Wednesday 9 May 2012
Room 210-211  16:00 - 18:00 Moderators: Angelique Louie, A. Dean Sherry

16:00 0478.   
Hyperpolarized water as an MRI contrast agent: Feasibility of in vivo imaging in a rat model
Mark David Lingwood1,2, Ting Ann Siaw3, Napapon Sailasuta4, Osama A Abulseoud5, Henry R Chan4, Brian D Ross4, Pratip Bhattacharya4, and Songi Han1,3
1Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States, 2Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States, 3Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA, United States, 4Enhanced Magnetic Resonance Laboratory, Huntington Medical Research Institutes, Pasadena, CA, United States, 5Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States

In this presentation we demonstrate a new perfusion MRI technique that utilizes Overhauser dynamic nuclear polarization (DNP) to provide authentic image contrast through the continuous delivery of contrast agent-free hyperpolarized water in rats. Water is hyperpolarized via Overhauser DNP at room temperature in the 0.35 T fringe field of a 1.5 T MRI magnet and then quickly transferred to the subject in the center of the same magnet for imaging. Images with hyperpolarized water show clearly enhanced flow contrast for all injection locations, demonstrating that this technique holds promise for localized angiography or brain perfusion studies.

16:12 0479.   
A novel contrast agent detects tropoelastin fibers in atherosclerotic plaques
Alkystis Phinikaridou1, Marcelo E Andia1, Rafael Torres Martin De Rosales2, and Rene M Botnar2
1Imaging Sciences, King's College London, London, United Kingdom, 2King's College London

Studies of human vessels showed increased deposition of tropoelastin fibres, the precursor of cross-linked mature elastin, in atherosclerotic vessels, and particularly in ruptured plaques, as well as aortic aneurysm. Here, we sought to develop a novel gadolinium-based MRI contrast agent that would selectively bind to tropoelastin and in this way differentiate the de novo synthesized fibers that are present in the vascular wall only under pathological conditions from the mature cross-linked elastin that is normally present in the vessel wall.

16:24 0480.   
Fibrin targeted MRI allows staging of deep venous thrombosis and identifies thrombi amenable for thrombolysis
Marcelo E Andia1, Prakash Saha2, Steven Grover2, Andrea J Wiethoff1, Tobias Schaeffter1, Alberto Smith2, and Rene M Botnar1
1Division of Imaging Sciences and Biomedical Engineering, Kings College London, London, London, United Kingdom, 2Academic Department of Surgery, Cardiovascular Division, Kings College London, London, London, United Kingdom

The in vivo evaluation of the stage of organization of venous thrombosis could help guiding medical treatment and intervention. In this work we show that the use of EP-2104R, a fibrin specific contrast agent, provides valuable information on the stage of thrombus organization and allows identification of thrombus suitable for lysis.

16:36 0481.   T2 tracks microstructural changes in implantable, iron oxide-doped hyaluronic acid/collagen hydrogels for preclinical and regenerative medicine.
Bradley D Hann1, and Kevin M Bennett1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States

To facilitate the development of hydrogel scaffolds for tissue engineering and regenerative medicine applications, we have developed a technique to monitor the changes in hydrogel structure caused by cellular or enzymatic degradation in a biocompatible, hyaluronic acid/collagen hydrogel. Changes in macromolecular structure of hydrogels result in changes in aggregation state of bound iron oxide nanoparticles. We report T2 changes during enzymatic and cellular degradation that correlate with ultrastructural change measured with electron microscopy. Hydrogels are also detected in vivo with MRI.

16:48 0482.   
Gadolinium-based "Smart" MRI Probes for Enzyme-targeted Cancer Imaging
Prachi Pandit1, Deju Ye1, John Ronald1, Jianghong Rao1,2, and Brian Rutt1
1Radiology, Stanford University, Stanford, CA, United States, 2Chemistry, Stanford University, Stanford, CA, United States

Recently, significant efforts are being devoted to the development of “smart” magnetic resonance imaging contrast agents. A common strategy involves a T1 relaxivity change in response to the presence of a target. Our group has devised a novel platform for the development of “smart” probes based on biocompatible chemical reactions where Gd-containing molecules, under the control of disulfide reduction and/or enzymatic cleavage, get activated to form magnetic nanoparticles and thus provide enhanced relaxivity. We have assessed the MR properties of these “smart” probes in solution and in cellulo in breast cancer cells.

17:00 0483.   
Imaging modulation of tumor hypoxia in vivo using a nitroimidazole based T1 MR contrast agent
Praveen Gulaka1, Robert Trokowski2, Ralph P Mason3, Dean Sherry2, and Vikram D Kodibagkar1,4
1Joint Program in Biomedical Engineering, UT Arlington/UT Southwestern Medical Center, Dallas, Texas, United States, 2Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, 3Radiology, UT Southwestern Medical Center, Dallas, Texas, United States,4School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States

Hypoxia in tumors is known to affect radiation sensitivity and promote development of metastases. Therefore the ability to image tumor hypoxia in vivo could provide useful prognostic information and help tailor therapy. Previous research demonstrated in vitro and in vivo evidence for selective accumulation of a T1 shortening agent, a GdDOTA monoamide conjugate of 2-nitroimidazole (abbreviated as GdDO3NI), under hypoxia. In this work, we report differential response of tumor hypoxia to oxygen breathing in two prostate cancer sublines (AT1 and HI) of rat prostate adenocarcinoma as imaged using GdDO3NI, thus, showing utility in stratifying tumor response to hypoxia altering interventions.

17:12 0484.   Gluco-CEST of Cerebral Glucose Metabolism: Correlation with 31P MRS
Kai-Hsiang Chuang1, Fatima A Nasrallah1, Guilhem Pages2, Philip William Kuchel2, and Xavier Golay3
1MRI Group, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore, 2Mechanistic Systems-biology NMR Group, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore, 3Institute of Neurology, University College of London, United Kingdom

1H magnetic resonance imaging (MRI) coupled with chemical exchange saturation transfer (CEST) was used to measure 2-deoxy-D-glucose (2DG) and 2DG 6-phosphate (2DG6P) in the brains of anaesthetized rats. The gluco-CEST signal was compared with 2DG6P measured in vivo with 31P MRS under different levels of isoflurane and hypercapnia. Gluco-CEST reflected cerebral metabolism but the data needed to be interpreted with caution to account for signals variations that occurred with the initial concentration of glucose, pH and due to the time-dependent washout of glucose.

17:24 0485.   MR Imaging of U87Capital Greek DeltaEGFR Human Glioma Tumor Xenografts Using Targeted Signal-Amplifying Enzymatic System
Mohammed Salman Shazeeb1, Suresh Gupta1, and Alexei Bogdanov1,2
1Department of Radiology, University of Massachusetts Medical School, Worcester, MA, United States, 2Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, United States

Molecular MR imaging of tumors expressing the EGF receptor variant III (EGFRvIII) was carried out in rats implanted with U87ÄEGFR human glioma xenografts in brain. Following systemic administration, anti-EGFRvIII monoclonal antibody conjugates of deglycosylated horseradish peroxidase (HRP) and glucose oxidase (GOX), facilitated local binding and prolonged retention of a paramagnetic molecular substrate, diTyr-DTPA(Gd), to sites of EGFRvIII overexpression. Retention of contrast agent following conjugate administration resulted in signal enhancement that was similar to that observed in our earlier studies of Gli36ÄEGFR tumors. This further demonstrates the utility of a self-complementing enzymatic signal amplification system for EGFRvIII targeted imaging.

17:36 0486.   An enzyme-responsive PARACEST MRI contrast agent that "turns on" after catalysis
Dina V Hingorani1, and Mark D Pagel1
1Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

We have developed a PARACEST MRI contrast agent, Tm-DO3A-cadaverine, that can detect the enzyme activity of Transglutaminase (TGase). This enzyme is an important biomarker of tumor vascular normalization that can cross-link extracellular matrix proteins by coupling lysine and glutamine side chains. Unlike most other enzyme-responsive CEST agents that "turn off" CEST after enzyme cleavage of a covalent bond, Tm-DO3A-cadaverine "turns on" CEST after the creation of a covalent bond by TGase.

17:48 0487.   Microfabricated MRI pH microsensors
Gary Zabow1,2, Stephen Dodd1, and Alan Koretsky1
1LFMI, NINDS, National Institutes of Health, Bethesda, Maryland, United States, 2Physical Measurements Laboratory, NIST, Boulder, Colorado, United States

Microengineered multi-spectral contrast agents generate their different spectral signals due to their different geometrical shapes. If the microstructure shapes were to change dynamically in response to some local physiological condition, they could give a changing spectral, or “color”, signal that would effectively serve as a real-time readout monitoring the particular physiological condition of interest. Here we give an example of this, using microstructures based on pH-sensitive hydrogels that dynamically change their shape under different pH conditions, forming an MRI pH-meter.