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Held immediately following the
4th Annual Systems Integration in Biodefense, August 24-25, 2005

Day 2


Tuesday, August 23

MOLECULAR IMAGING

8:00-8:30 Morning Coffee

8:30-8:40 Chairperson’s Comments
Dr. Carol Dahl, Director for Global Health Technologies, Bill and Melinda Gates Foundation 

8:40-9:10 Nanoparticle-Based Molecular Imaging Agent for Diagnosis in Neovascular Diseases
Dr. Shelton D. Caruthers, Senior MR Clinical Scientist, Philips Medical Systems and Associate Director, Cardiovascular Magnetic Resonance Laboratories, Washington University School of Medicine 
As biotechnology advances, in vivo imaging is rapidly incorporating microscopic and biochemical information. Similarly, the evolving paradigms of medicine are growing toward the in vivo characterization of the molecular mechanisms of disease with high-affinity, targeted ligands affording a targeted diagnosis. Utilizing these converging technologies, the nanoparticle-based molecular imaging agent presented here provides a high-affinity, target-directed diagnostic imaging agent with the potential of additionally monitoring drug delivery and response. Based on a perfluorocarbon emulsion, this nanoparticle system has been applied successfully in models of neovascular disease such as atherosclerosis and tumor growth.

9:10-9:40 Quantum Dots Co-Localize with Glioma
Steven A. Toms, MD, MPH, Director, Section of Metastatic Disease, Brain Tumor Institute, Cleveland Clinic Foundation
The use of fluorescent semiconductor nanocrystals (Quantum Dots) for in vitro and in vivo biological applications has been rapidly evolving. A major difficulty with nanoparticles is phagocytosis by components of the reticuloendothelial system, which limits circulation half-life of nanoparticles and impedes specific tissue targeting by conjugated nanocrystals. Surface coating of the nanocrystals with long chains of polyethylene glycol (PEG) improves the circulation half-life and permits phagocytosis of the circulating nanocrystals by tissue macrophages. Tissue macrophages and microglia infiltrate experiment glioma and accurately outline tumor borders. Intravenous delivery long chain PEG coated Quantum Dots is accompanied by phagocytosis by macrophages and microglia, allowing the optical imaging of brain tumors which may allow more accurate biopsy and resection of gliomas.

9:40-10:10 In Vivo Optical Imaging Enabled by Soft-Matter Analogues of the Quantum Dots
Dr. Michael J. Therien, Alan G. MacDiarmid Professor of Chemistry, University of Pennsylvania 
In aqueous solution, hydrophobic conjugated-multi(porphyrin)-based near-infrared fluorophores (NIRFs) cooperatively self assemble with amphiphilic diblock copolymers to form polymersomes (100 nm diameter polymer vesicles). The thick membranes of these synthetic vesicles uniquely segregate and uniformly disperse large numbers of high emission dipole strength NIRFs. Extrusion methods enable isolation of NIR-emissive polymersomes having homogeneous, nanoscale, size distributions. Long-wavelength optical excitation of such assemblies generates intense, highly localized emissive signals capable of penetrating through the dense tumor tissue of a live animal. The stability of these synthetic vesicles, coupled with the ability to modulate their emission over a 600-to-950 nm wavelength domain, define a family of nanometer-sized emissive soft matter that offers an intriguing complement to in vivo imaging platforms based on quantum dots, with exceptional potential to facilitate deep-tissue diagnostic and drug-delivery applications.

10:10-10:40 Coffee Break, Poster & Exhibit Viewing

10:40-11:10 Nanoshells for Molecular Targeted Imaging and Therapy of Cancer
Dr. Rebekah Drezek, Stanley C. Moore Assistant Professor, Bioengineering, Rice University
We describe initial results of our work towards the development of targeted gold nanoshells for combined imaging and therapy applications. Metal nanoshells consist of a silica core coated with a thin layer of gold. These particles provide an ideal material for many biomedical imaging and therapy applications because the optical resonance can be precisely tuned to desired wavelengths through the visible and near infrared spectral regions by varying the core/shell thickness ratio. In a proof-of-principle study, we demonstrate that it is possible to fabricate biocompatible immunotargeted gold nanoshells which exhibit favorable scattering properties for imaging at one wavelength and a high absorption cross-section required for photothermal therapy at a second wavelength. The results of initial in vitro cell studies and in vivo animal experiments will be presented.

11:10-11:40 Nanosensors and Biochips: From Research Bench to Clinical Settings
Dr. Tuan Vo-Dinh, Corporate Research Fellow, Group Leader, Advanced Biomedical Science and Technology Group (ABSTG), Director, Center for Advanced Biomedical Photonics (CABP), Oak Ridge National Laboratory
This presentation discusses the development and application of advanced nanosensors, nanoprobes, and biochips for biomedical diagnostics. Combining the exquisite specificity of biological recognition probes and the excellent sensitivity of laser-based optical detection, nanoprobess are capable of detecting and differentiating biochemical constituents of complex systems for bioimaging. The development of nanosensors opens new horizons to biomolecular research at the single-cell level, and permits the ability to probe the intact cellular architecture. Recently, we have developed a novel integrated Multi-functional Biochip (MFB) which allows simultaneous detection of several disease end-points using different bioreceptors such as DNA, antibodies, enzymes, cellular probes) on a single biochip system. The biochip has recently been developed to detect the gene fragments of Tuberculosis and the HIV gene system as well as the p53 and FHIT proteins. The biochip could be used to diagnose genetic susceptibility and diseases, or to monitor exposure to bioactive environmental samples. Technology transfer activities of the MFB technology to the private companies (HealthSpex, Nanodetection Technologies) for the development of a new, Inexpensive System for the simultaneous detection of multiple genetic mutations in a range of clinical and non-clinical settings will be discussed.

11:40-12:10
“Advantages of Nanoparticles for Molecular Imaging”

 

12:10-1:30 Lunch on your own
(Technology Workshop Sponsorship Available)

DRUG DELIVERY SYSTEMS IN THE CLINIC

1:30-1:40 Chairperson’s Comments
Chairperson: Dr. Mauro Ferrari, Associate Vice President for Health Sciences, Technology, and Commercialization, and Associate Director,Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University

1:40-2:10 Delivery Strategies for Targeted Therapy
Dr. Barrett E. Rabinow, Director of Strategic Development, Baxter Healthcare 
Delivery strategies of nanoparticles for targeted therapy involve passive and active modes following injection, as well as direct delivery to particular sites. Examples will be discussed involving monocyte phagocytic system targeting of slow dissolving nanoparticles for the purpose both of altering pharmacokinetics of the drug, as well as for targeting of liver and macrophage mediated-diseases. Prolonged circulation time enabled by coating with hydrophilic surfactants permits passive targeting to sites of tumor, infection, and inflammation. Coating of nanoparticles with particular ligands permits active targeting to specific cell types, such as brain endothelial cells, hepatocytes or tumor cells; and to intracellular regions such as cytoplasmic space vs. endosomal vesicles; as well as to regions of the body affected by local heating or irradiation. Direct delivery to the ventricles of the brain and the pulmonary space, as well as the prospects for nanoparticulate targeting following oral delivery will also be discussed.

2:10-2:40 Nanotech Constructs in Drug Delivery
Dr. William Van Antwerp, Distinguished Scientist, Corporate Science & Technology, Medtronic MiniMed 
We will discuss the applicability of nanotechnology constructs in drug delivery. Our view is that nano-based materials will be prominent in drug delivery in 5 years, while self assembly-based construct will be much longer out.

2:40-3:10 A Dendrimer in the Clinic: A Dendrimer-Based Microbicide Targeted at Prevention of HIV
Dr. Jeremy Paull, Regulatory Affairs and QA Manager, Starpharma Pty Ltd.
Starpharma is developing defined and precise dendrimer nanostructures as targeted drugs, and has just completed the world’s first clinical trials under US FDA regulations of its lead development candidate, the dendrimer, SPL7013 for prevention of HIV infection in women. SPL7013 is a poly-anionic, lysine dendrimer with a molecular weight of 16.5 KDa. The development of SPL7013 has been supported by the development of regulatory standard analytical and bioanalytical methods. The dendrimer is designed to have efficacy against HIV and other sexually transmitted infections, while being safe to the user. In the clinical trial, SPL7013 Gel (VivaGel) when applied intravaginally in healthy women was shown to be safe and well tolerated, and there was no systemic absorption. The study shows that the dendrimer is localised at the site of delivery for optimum disease targeting and safety profile.

3:10-3:40 Refreshment Break, Poster & Exhibit Viewing

3:40-5:00

STRATEGIC DISCUSSION: Getting Nanoparticles Ready for the Clinic
Chairperson: Dr. Mauro Ferrari
Mr. Alex W. Kawczak, Vice President, BioProducts and Nanostructured Materials, Laboratory Operations/Commercial Business, Battelle Memorial Institute 

Mr. Bob Root, Chief Executive Officer, Orion Group Inc.
Dr. Lloyd L. Tran, President, International Association of Nanotechnology

5:00 End of Conference


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