|New Cellular & Molecular Imaging Agents|
Dual Transfer of Gene and MR Contrast Agent Into
Stem-Progenitor Cells for in Vivo MR Imaging of Stem Cell-Mediated Gene
Bensheng Qiu1, Xiangcan Zhan2, Piper Treuting1, Charles W. Frevert1, Xiaoming Yang1
1University of Washington, Seattle, Washington, USA; 2Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Atherosclerotic cardiovascular disease is a unique illness that produces diffuse and multiple atherosclerotic lesions in nearly all arteries of the body. Hematopoietic stem-progenitor cells circulate in the blood system, flow through the entire body, and thus home to wherever atherosclerotic plaques exist. Transfer of therapeutic genes into hematopoietic stem-progenitor cells prior to their transplantation to the body may enable to explore a stem cell-mediated target-specific delivery of therapeutic genes. This study focused on validation of the feasibility to co-transfer a reporter gene and an MR contrast agent into bone marrow (BM) cells in vitro and in vivo, which should establish the groundwork to develop target-specific molecular MR imaging of stem-progenitor cell-mediated gene therapy of atherosclerotic cardiovascular diseases.
Hyperpolarized 3He MRI to Detect Lung Metastases
Targeted by Magnetic Nanoparticles
Tamara Branca1, Carola Leuschner2, Challa Kumar2, Boma Fubara3, Warren Warren1, Bastiaan Driehuys3
1Duke University, Durham, North Carolina, USA; 2Louisiana State University, Baton Rouge, Louisiana, USA; 3Duke University Medical Center, Durham, North Carolina, USA
We demonstrate a novel method to detect the accumulation of targeted nanoparticles in lung cancer metastases by using 3He MRI. A BALB/c mouse was inoculated with MDA-MB-435S human breast cancer cells, which after 60 days resulted in metastatic cells in the lungs. The mouse was injected 24 hr prior to imaging with super paramagnetic iron oxide nanoparticles (SPIONs) that were conjugated with the lutenizing hormone releasing hormone (LHRH) whose receptors are over-expressed by breast cancer cells. Hyperpolarized 3He lung images made at TE=4 ms contained numerous signal voids that were shown histologically to be regions of SPION accumulation.
Charged Nanoparticles for MRI of the
Kevin M. Bennett1, Hua Zhou2, James P. Sumner1, Stephen J. Dodd1, Nadia Bouraoud1, Kent Doi2, Robert A. Star2, Alan P. Koretsky3
1National Institute of Neurological Disease and Stroke, Bethesda, Maryland, USA; 2National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, Maryland, USA; 3National Institutes of Neurological Disease and Stroke, Bethesda, Maryland, USA
In this work, a method for noninvasively detecting the integrity of the basement membrane, based on the delivery of cationic iron-oxide nanoparticles, was developed. Particles accumulate due to the highly negative charge of the basement membrane. After systemic injection of cationic (CF) or native (NF) ferritin, ex vivo and in vivo MRI showed selective accumulation of CF in kidney glomeruli. . Immuno-fluorescence and electron microscopy confirmed that CF was localized to the glomerular basement membrane (GBM). In a model of GBM breakdown, MRI showed reduced single glomerular accumulation of CF, but a diffuse accumulation of CF in the kidney cortex
An MRI Contrast Agent Targeted for Activated
Platelets Allows Detection of Thrombosis and Thrombolysis in an in Vivo
Dominik von Elverfeldt1, Constantin von zur Muhlen1, Julia Moeller1, Dominik Paul1, Anne Katrin Becker1, Irene Neudorfer1, C Bode1, K Peter2, Juergen Hennig1
1University Hospital Freiburg, Freiburg, Germany; 2Baker Heart Research Institute, Melbourne, Australia
To allow in vivo imaging of activated platelets in wall adherent, non-occlusive carotid thrombosis, we applied an MRI contrast agent consisting of MPIOs and single-chain antibodies designed to selectively recognize ligand-induced binding sites of the activated GPIIb/IIIa-receptor. We were able to image wall adherent thrombosis and directly monitored the success of thrombolytic treatment. The contrast agent represents a novel and unique technique that allows detection and quantification of thrombi and can be used to monitor success of thrombolytic therapy. These properties are a promising basis for further development of MPIO-based contrast agents for the potential detection of vulnerable atherosclerotic plaques.
MRI-Invisible Pathology in Murine Cerebral Malaria
Revealed by a Novel Contrast Agent Recognising Activated Platelet
Glycoprotein IIb/IIIa Receptors
Nicola Sibson1, Constantin von zur Mühlen1, 2, Karlheinz Peter3, Robin Choudhury1, George Grau4, Christoph Bode2, Sandra Campbell1, Daniel Anthony1
1University of Oxford, Oxford, UK; 2University Hospital Freiburg, Germany; 3Baker Heart Institute, Melbourne, Australia; 4The University of Sydney, Australia
Neurological MRI is often limited in that it reflects downstream injury, and it cannot assess disease activity. Molecular imaging has the potential to overcome these limitations. Human and murine cerebral malaria are associated with increased cytokines in the brain and adherence of platelets to the microvasculature. Here, we demonstrate that platelet accumulation in the brain microvasculature can be detected with MRI using a novel contrast agent targeted at ligand-induced binding sites on activated platelet GPIIb/IIIa receptors at a time when the pathology is otherwise undetectable. These results highlight the potential of targeted contrast agents for diagnostic, mechanistic and therapeutic studies.
Novel Single Layer MR-Visible Alginate Microcapsules
for Visualization and Immunoprotection of Hepatocytes
Thomas Link1, 2, Partha Hota1, Brad P. Barnett1, Chris M. Long1, 2, Segun Bernard1, Piotr Walczak1, Robert Liddell1, Aravind Arepally1, Jeff Bulte1
1Johns Hopkins Medical Institution, Baltimore, Maryland, USA; 2Johns Hopkins University, Baltimore, Maryland, USA
Feridex was incorporated into novel single layer barium cross-linked alginate microcapsules to create MR-visible magnetocapsules for immunoprotection of hepatocytes. Capsule MRI properties were assessed using gelatin phantoms and cell viability was assessed in vitro. Results indicate that capsule permeability and cell viability were similar to standard alginate-PLL-alginate magnetocapsules. MRI properties were also similar, demonstrating their potential for use in vivo for treatment of fulminant liver failure.
Lipid-Coated Silica Nanoparticles; a
Contrast Agent Platform for Multimodality Molecular Imaging
Rolf Koole1, Matti M. van Schooneveld1, Jan Hilhorst1, Karolien Castermans2, Gustav J. Strijkers3, Celso de Mello Donegá1, Daniel Vanmaekelbergh1, Arjan W. Griffioen2, Klaas Nicolay3, Zahi A. Fayad4, Andries Meijerink1, Willem J. M. Mulder4
1Utrecht University, Utrecht, Netherlands; 2Maastricht University, Maastricht, Netherlands; 3Eindhoven University of Technology, Eindhoven, Netherlands; 4Mount Sinai School of Medicine, New York, USA
A novel platform for multimodal contrast agents is presented, based on a hydrophobic silica particle with a lipidic coating. It describes a general method for making silica particles bio-applicable. Here, we used quantum dots incorporated in silica particles, coated by a layer of paramagnetic, pegylated, and bio-functional lipids. The particles are highly target-specific, and can be used for both fluorescence imaging and MRI.
Improved Molecular Imaging of Angiogenesis by
Synergistic Targeting of Liposomal Contrast Agent to the Receptors α ν β
3 Integrin and Galectin-1
Ewelina Kluza1, Daisy van der Schaft1, Willem Mulder2, Arjan Griffioen3, Gustav J. Strijkers1, Klaas Nicolay1
1Eindhoven University of Technology, Eindhoven, Netherlands; 2Mount Sinai School of Medicine, New York, USA; 3Maastricht University & The University Hospital Maastricht, Maastricht, Netherlands
Tumor angiogenesis has become an important target in tumor diagnostics and anti-tumor therapy. We propose targeting of two receptor populations:α vβ 3integrin and Galectin-1 in order to increase the delivery of the paramagnetic contrast agent to activated endothelial cells. Two ligands, cyclic RGD peptide and Anginex, were conjugated to paramagnetic/fluorescent liposomes. Fluorescence microscopy, fluorescence intensity measurements and T1 relaxation time measurements showed that the uptake of liposomal contrast agent by angiogenic endothelial cells was increased by simultaneous targeting of two receptor populations. This appeared to be the most effective by conjugating two different ligands to the same particle.
Urokinase Plasminogen Activator Receptor (UPAR)
Targeted Multifunctional Magnetic Nanoparticles for in Vivo Molecular
MRI of Pancreatic Cancers
Hui Mao1, 2, Lily Yang1, 2, Xianghong Peng2, Chunchun Ni3, Andrew Y. Wang4, Shuming Nie1, 2, Xiaoxia Wang1
1Emory University School of Medicine, Atlanta, USA; 2Emory University, Atlanta, USA; 3Emory University School of Medicine, Atlanta, Georgia, USA; 4Ocean NanoTech LLC, Fayetteville, USA
We are reporting an novel nanoparticle based receptor targeted imaging agent for imaging pancreatic cancer in the animal model
In Vivo and in Vitro Mapping of the Radio
Frequency Magnetic Field Generated by Microsized Resonators in a 3T
Clinical MRI Scanner
Razvan Ciocan1, Robert E. Lenkinski1, Jonathan Bernstein2, Robert Marquis1, Alex Ivanishev1, Aya Matsui1, Fotini Kourtelidis1, Mirela Bancu2, Jeffrey T. Borenstein2, John V. Frangioni1
1Beth Israel Medical Center, Boston, Massachusetts, USA; 2The Charles Stark Draper Laboratory, Boston, Massachusetts, USA
Micro-sized resonators can provide a way of individual cell tracking in a clinical MRI. In this work we demonstrate that magnetic field generated by such devices that have the dimensions 300, 500, and 1000 microns, respectively, can be mapped in experiments performed in a clinical 3T scanner.