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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.

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.

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

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.

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.

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.

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.

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.

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

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.