Novel Contrast Agents & Labels
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Tuesday May 10th
Room 518-A-C  16:00 - 18:00 Moderators: David P. Cormode and Mark Pagel

16:00 314.   In vivo MR CEST imaging of the Viability of Microencapsulated Cells 
Kannie Wai Yan Chan1,2, Xiaolei Song1,2, Guanshu Liu1,3, Dian Arifin1,2, Heechul Kim1,2, Chulani Galpoththawela1,2, Ming Yang4, Justin Hanes4,5, Assaf Gilad1,2, Piotr Walczak1,2, Jeff W. M. Bulte1,2, and Michael T McMahon1,3
1Russell H. Morgan Department of Radiology and Radiological Sciences, 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 Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States,5Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Semi-permeable microcapsules have been used previously to immunoprotect and visualize therapeutic cells after transplantation. We have constructed pH-sensitive microcapsules which generate CEST contrast dependent on the local physicochemical microenvironment. These capsules can be tracked and also used as a unique way to monitor cell viability through MRI. In this study, we have tested whether or not our new CEST microcapsules could monitor the viability of hepatocytes expressing luciferase both in vitro and in vivo. We observed a decrease in CEST contrast with decreasing hepatocyte viability upon administration of STS in vitro and also after subcutaneous transplantation into mice, as validated with bioluminescent imaging.

16:12 315.   Measuring in vivo tumor pHe with a DIACEST MRI contrast agent 
Liu Qi Chen1, Vipul R Sheth2, Christine A Howison3, Phillip H Kuo4, and Mark D Pagel5
1Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 2Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States,3Arizona Research Laboratories, University of Arizona, Tucson, AZ, United States, 4Radiology, Medicine, Biomedical Engineering, University of Arizona, Tucson, AZ, United States, 5Biomedical Engineering and Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

Ultravist®, a contrast agent that is clinically approved for X-ray/CT imaging, can also serve as a DIAmagnetic CEST (DIACEST) MRI contrast agent. A ratio of the two CEST effects from Ultravist® can be used to measure pH over a range of 6.2-7.4 pH units with a precision of 0.070 pH units. This ratiometric approach obviates the need to know the agent's concentration or sample's T1sat relaxation time when measuring pH. We have used this DIACEST agent and a CEST-FISP MRI method to measure the extracellular pH (pHe) within a subcutaneous tumor and muscle of a mouse model of PANC-1 pancreatic cancer.

16:24 316.   CEST Imaging Reveals Dynamic Changes of Implanted Hydrogel Scaffold in Vivo 
Yajie Liang1,2, Amnon Bar-Shir1,2, Xiaolei Song1,2, Assaf A Gilad1,2, Jeff W.M Bulte1,2, and Piotr Walczak1,2
1Division of MR Research, Russell H. Morgan Dept. of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, 2Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Chemical Exchange Saturation Transfer (CEST) MRI was used to monitor hydrogel scaffold that is now widely applied in encapsulation of stem cells for transplantation studies. By correlating bioluminescent imaging and histological results, we demonstrated that changes in CEST signals in vivo over time could allow monitoring molecular gel composition and potentially provide new insights on mechanism underlying cell migration in scaffold after transplantation. Along with the increasing use of biomaterials encapsulating stem cells in regenerative medicine, CEST MRI could be a valuable tool in investigation of dynamic changes in scaffold materials in the context of cell transplantation in vivo.

16:36 317.   Study axonal transport rate and neuronal turnover rate of the olfactory system using novel MRI anatomical contrast agent GdDOTA-CTB 
Carolyn W.-H. WU1, Olga Vasalatiy2, Leslie G Ungerleider3, and Gary Griffiths2
1NeuroSpin / CEA, Gif Sur Yvette, Île-de-France, France, 2IPDC /NHLBI / NIH, Rockville, MD, United States, 3LBC /NIMH /NIH, Bethesda, MD, United States

Understanding neuron functions including axonal transport and metabolic clearance rats are important to study why the diseased brains are malfunctional. Our recent developed MRI visible contrast agent GdDOTA-CTB allows longitudinally monitoring monosynaptically anatomically connected brain circutary. In this study we further test its application to study axonal transport and neuronal turnover in the olfactory system. This study will open the new possibility to study the olfactory related malfunctions in various neurodegeneration diseases.

16:48 318.   Direct Albumin Imaging in Mouse Tumour Model 
Jamu K. Alford1, Christian T. Farrar1, Yan Yang1, William Bradfield Handler2, Blaine A. Chronik2, Timothy J Scholl3, Gunjan Madan4, and Peter Caravan1
1Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 2Physics and Astronomy, The University of Western Ontario, London, ON, Canada, 3Department of Medical Biophysics, The University of Western Ontario, London, ON, Canada, 4Siemens Medical Solutions Inc., Malvern, PA, United States

We present the first example of direct protein imaging in a living animal. Delta relaxation enhanced MR (dreMR) is a method that exploits the strong magnetic field dependence of slow-tumbling gadolinium-based contrast agents. A 1.5T, clinical MRI was outfitted with an actively shielded electromagnet to dynamically control the magnetic field in the imaging region. A nude mouse implanted with LS174T tumors was imaged within the electromagnetic insert using the albumin-bindin agent MS-325. Using the insert, the B0 field was varied from 1.4T to 1.6T to produce images of albumin distribution throughout the mouse.

17:00 319.   A novel fluorine relaxation switch for tracking the binding and intracellular processing of molecularly targeted nanoparticle contrast agents 
Lingzhi Hu1, Junjie Chen1, Shelton D Caruthers1, Gregory M Lanza1, and Samuel A Wickline1
1Washington University in St. Louis, St. Louis, MO, United States

In the field of molecular imaging with nanoparticle contrast agents, it would be advantageous to know not only that a particle binds to its target but also that it is internalized and subsequently processed and sorted to the subcellular compartment.Here we develop an analytical description and experimental validation of 19F longitudinal T1 relaxation as an indicator for assessing the integrity of paramagnetic PFC NP. When Gd is stripped from the nanoparticle surface, a “relaxation switch” occurs revealing the transition from intact bound particle to processed constituents.

17:12 320.   Specific Targeting of EGF Receptor Expression with Monoclonal Antibody Conjugates in Human Gliomas Using MRI 
Mohammed Salman Shazeeb1,2, Christopher Howard Sotak1,3, and Alexei Bogdanov, Jr.3,4
1Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, United States, 2Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA, United States, 3Radiology, University of Massachusetts Medical School, Worcester, MA, United States, 4Cell biology, University of Massachusetts Medical School, Worcester, MA, United States

Specific targeted EGF receptor imaging in Gli36 tumor xenografts implanted in the rat brain was achieved using anti-EGFR monoclonal antibody conjugates (mACs) that facilitate local binding of a paramagnetic molecular substrate diTyr-DTPA(Gd) at the EGFR/EGFRvIII-overexpressing sites. Following anti-EGFR mAC administration, diTyr-DTPA(Gd) was retained for a significantly longer period of time as compared to the administration of the contrast agent without mAC or with anti-EpCAM mAC pre-treatment. Retention of diTyr-DTPA(Gd) following anti-EGFR mAC administration is consistent with enzyme-mediated coupling of the paramagnetic agent to EGFR/EGFRvIII-overexpressing cells in the tumor allowing effective MRI visualization of conjugate co-localization at the targeted site.

17:24 321.   High R1 of Mn2+ adsorbed to hydrophilic pores of magnetoferritin nanoparticles 
Veronica Clavijo Jordan1, and Kevin M Bennett1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States

The enhancement of R1 due to paramagnetic ions can be modulated by controlling the sequestration and exchange of water protons around the ion. Here we report a new synthesis technique to enhance R1 by strategic placement of manganese (II) ions on the surface hydrophilic channels of apoferritin, causing a strong increase in R1. The results indicate that these manganese ions, when clustered in such channels on a highly filled apoferritin cavity (magnetoferritin), can create a per-ion R1 of 330mM-1s-1.

17:36 322.   Quantitative assessment of macrophage activity in inflammatory bowel disease using fluorine-19 MRI and the response to treatment 
Deepak K Kadayakkara1,2, and Eric T Ahrens1,2
1Carnegie Mellon University, Pittsburgh, PA, United States, 2Pittsburgh NMR Center for Biomedical Research, Pittsburgh, PA, United States

In this study, we characterize inflammatory burden in a mouse model of inflammatory bowel disease (IBD) by in situ macrophage labeling using perfluorocarbon emulsion. Using fluorine-19 MRI, changes in bowel inflammation and macrophage activity in response to treatments are monitored non-invasively in vivo. In vivo MRI results are validated by ex vivo MRI of the excised colon samples, confocal microscopy, histology score and qRT PCR analysis of macrophages. Our results demonstrate that fluorine-19 MRI is an effective method to quantitatively measure macrophage activity in vivo and assess treatment response in IBD.

17:48 323.   In vivo MR imaging of macrophages in cardiac ischemia/reperfusion injury with paramagnetic phosphatidylserine-containing liposomes 
Tessa Geelen1, Sin Yuin Yeo1, Leonie E Paulis1, Bram F Coolen1, Klaas Nicolay1, and Gustav J Strijkers1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

After a myocardial infarction, macrophages infiltrate the damaged tissue to remove dead cells and promote left ventricular remodeling. The aim of this study was to characterize the presence of these macrophages with MRI. Phosphatidylserine (PS) was incorporated in paramagnetic liposomes to promote uptake by macrophages. In vitro, liposomes containing 6 mol% PS showed the highest uptake by murine macrophages. These liposomes were applied after mouse cardiac ischemia/reperfusion injury and visualized with T1-weighted MRI and confocal microscopy. PS-liposomes were specifically associated with macrophages in the infarcted myocardium 2.5 hours after injection. After 24 hours of circulation, passive accumulation was predominant.