Tuesday, November 14
Shared Session with Fluorescent Proteins in
Drug Development
7:15 Registration and Morning Coffee (Sponsorship for Breakfast Workshop Available)
8:25 Chairperson’s Opening Remarks
Richard Levenson, M.D., Director of Research, Biomedical Systems, CRI, Inc.
| Keynote Presentation |
8:30 Molecular Imaging: From Research through Drug Discovery to the Clinic-Defining Path Forward
Peter Lassota, Ph.D., Vice President,
Oncology, Caliper Life Sciences |
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Optical Imaging
9:15 In Vivo Optical Imaging Enabled by Soft-Matter Analogues of the Quantum Dots
Michael Therien, Ph.D., Professor of Chemistry, University of Pennsylvania
Formed through cooperative self-assembly of amphiphilic diblock copolymers and electronically conjugated porphyrinic near infrared (NIR) fluorophores, NIR-emissive polymersomes (50 nm 50 um polymer vesicles) define a family of organic-based, soft matter quantum dot analogues that are ideally suited for in vivo optical imaging. We show that membrane incorporation of a wide range of related multi-porphyrinic fluorophores enables emission energy modulation over a broad domain of the visible and near infrared spectrum (600-950 nm). Long-wavelength optical excitation of such assemblies generates intense, highly localized, emissive signals capable of penetrating through the dense tumor tissue of live animals. New nanoscale polymersomal vesicles in which the component amphiphilic diblock polymers are derived from two previously FDA-approved building blocks have been delineated, providing for fully bioresorbable probes. Excited-state transient dynamical studies provide insights into how NIR-emissive polymersomes can be further optimized for in vivo deep-tissue fluorescence-based imaging.
Bioluminescence
9:45 Combining Bioluminescent Reporters and Fluorescent Probes for Studying Tumor Growth and Biology in Mouse Xenograft Studies
Steven Smith, Ph.D., Senior Scientist, Xenogen Corporation, a Caliper
Life Sciences Company
Luciferase-based reporters have been widely adopted for studying tumor growth and metastasis in xenograft models. Cells constitutively expressing luciferase (luc) are particularly useful for non-invasively tracking and monitoring the growth of the primary tumor and identifying metastases. Additionally, inducible luc reporters, and specially designed constructs of luc, assay other aspects of tumor biology such as inhibition of the proteasome by drugs, or the induction of angiogenesis. Fluorescent probes provide another imaging tool that complements bioluminescent imaging. Organic fluorophores can be used to tag protein and peptide ligands, antibodies, and small molecules and these are used to track the presence of extracellular proteins/receptors/enzymes in vivo. Additionally, activity based probes incorporating fluorescence are used to evaluate enzyme activity. Combining bioluminescent and fluorescent imaging modalities in the same xenograft models allows the investigator to probe many aspects of tumor biology simultaneously.
10:15 Coffee Break in the Exhibit Hall
11:00 In Vivo Bioluminescence Imaging Predicts FLT-PET Response to Novel Combination Therapy
Kenna Anderes, Ph.D., Associate Director Cancer Biology, Pfizer, Inc.
The ability to accurately predict which experimental therapies or combination therapies will provide clinical benefit remains a dark art. Bioluminescence imaging (BLI) sheds light on active agents and may predict FLT-PET responses. Correlative studies were conducted using BLI and FLT-PET imaging in xenografts used to evaluate novel combination therapies.
11:30
TBA
Kohkan Shamsi M.D., Ph.D., President, Symbiotic Pharma Research
Preclinical Imaging
12:00 In Vivo Cellular MRI: Tracking Magnetically Labeled Cells in Disease Models
Joseph Frank, M.D., Chief, Experimental Neuroimaging Section, National Institutes of Health
Mammalian stem cells or other cells are being considered for infusion or transplantation into tissue for purposes of repair, regeneration or other therapeutic approaches. Cellular Imaging is a valuable tool for monitoring cell migration and trafficking in vivo. Magnetic labeling of cells provides the ability to monitor their temporal spatial migration in vivo cellular MRI. The techniques for labeling cells with MRI contrast agents have been well established in experimental systems and are presently being translated to the clinic. In this presentation, I will describe the different approaches used to label cells with contrast agents and show MRI and histological results in various animal disease models. Magnetic Tagging of cells has the potential for guiding future cell-based therapies in humans and for the evaluation of cellular based treatment effects in disease models.
12:30 Luncheon Technology Workshop:
Translational Applications of Optical, MultiModal In Vivo Molecular Imaging
Shahram Hejazi, Ph.D., WW General Manager, Molecular Imaging
Systems, Kodak Health Group
William E. McLaughlin, Director of R&D, Kodak Molecular Imaging Systems
Exciting new molecular imaging agents enable highly specific fluorescent, luminescent, and radioisotope imaging of disease processes within living animals. These in vivo molecular imaging agents provide the potential for rapid detection of specific changes within the target tissues long before morphological changes from disease or from disease treatment are present. Use of these imaging agents in live animals has stimulated the development of multi-modal image systems, the application of which will be presented. |
Sponsored by
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1:55 Chairperson’s Remarks
2:00 In Vivo Preclinical Imaging in Drug Discovery
Matthew Silva, Ph.D., Scientist, Imaging Science, Millennium Pharmaceuticals, Inc.
The generally accepted role for medical imaging in preclinical pharmaceutical drug discovery and development is to assist in the advancement of animal disease models and to provide additional drug efficacy read-outs. The successful implementation of this strategy requires (1) the full commitment of the institution to support the imaging group and (2) the keen ability of imaging scientists to identify impact projects. This talk focuses on the integration of a multi-modal, small animal, in vivo imaging facility into the drug development processincluding project prioritization, “pharmaceutical-grade” throughput, assay robustness, and drug efficacy measurements.
2:30 Imaging Wortmannin: New Sights For an Old Molecule
Lee Josephson, Ph.D., Associate Professor, Center for Molecular Imaging Research, Harvard Medical School
The ability to image the fate of natural products in biological systems can provide valuable information about their behavior, and further development of drug leads based on this important source of materials for pharmaceutical development. Fluorescent forms of wortmannin, a natural product inhibitor of PI3 Kinase, provide insights into the mechanism of wortmannin action and development of wortmannin based inhibitors of this enzyme, which plays an important role in controlling cell proliferation. In collaboration with Katie Barnes, Hushan Yuan, and Ralph
Weissleder.
3:00 In Vivo Molecular Imaging of Spatio-Temporal Drug Distribution Using the Sub-Millimeter
NanoSPECT/CT
Jeffrey P. Norenberg, MS, PharmD, BCNP, FASHP, FAPhA, Executive Director, National Association of Nuclear Pharmacies, Associate Director, New Mexico Center for Isotopes in Medicine, Associate Professor and Director, Radiopharmaceutical Sciences, College of Pharmacy, and Jack Hoppin, Ph.D., Vice
President, Imaging Systems, Bioscan, Inc.
We will present descriptions and results of numerous in vivo bio-distribution studies using radio-labeled pharmaceuticals. The talk will describe the imaging capabilities of the four-headed
NanoSPECT/CT system including discussions of resolution, sensitivity and uptake quantification capabilities. We will present results of initial pharmacokinetic studies performed with the NanoSPECT demonstrating the new-found strength of temporal imaging with multi-pinhole
SPECT.
3:15 Solutions Showcase Get informed on the newest technology and developments.
Contact Carol Dinerstein at 781-972-5471 for sponsorship opportunities.
4:30 In Living Color: Multispectral In Vivo Imaging
Richard Levenson, M.D., Director of Research, Biomedical Systems, CRI, Inc.
Small-animal imaging has a number of goals: high sensitivity, quantitative accuracy, multiplex capability, depth information, high throughput, ease-of-use, physiological animal positioning, high experimental throughput, and so on. The Maestro™ multispectral imaging system addresses many of these issues. One of the barriers to sensitive detection and quantitation is the presence of abundant tissue autofluorescence in the intact (skin-on) mouse. Multispectral imaging, combined with algorithms that can “unmix”, or separate, signals, results in targets appearing displayed against a black, near-zero background. Improvements in sensitivity of as much as 300-fold have been demonstrated compared to conventional imaging systems. While moving to the NIR can reduce
autofluorescence, this strategy limits the potential for signal multiplexing. However, a multispectral approach allows for the simultaneous detection of at least 5 different spectrally and spatially overlapping fluorescent signals. Finally, accurate spectral unmixing allows the detection and measurement of fluorescent signals as dim as 5% of the autofluorescent signal “floor.”
5:00 Modeling and Treating Immune-Mediated Diseases Using
In Vivo Imaging of Transgenic Zebrafish
Nikolaus S. Trede, M.D., Ph.D., Assistant Professor of Pediatrics, Investigator, The Huntsman Cancer Institute, University of Utah
Among the many advantages zebrafish offer is their transparency during early development and their small size. These features make it an attractive model for in vivo imaging. We have generated a transgenic line of zebrafish where all T cells are GFP labeled. Using multispectral imaging technology we are able to follow the development, migration, and accumulation of T cells from larval to adult stages. We have also initiated a mutagenesis screen, where we identified immunodeficient and leukemic phenotypes that are now the subject of detailed analysis and positional cloning. In addition, we have started a small molecule screen to identify compounds with anti-T cell activity. With our transgenic line we can screen through roughly 1,000 compounds each week. These approaches will be instrumental to our understanding of the molecular basis of leukemia and may contribute to more targeted therapies for this life-threatening disease.
5:30 In Vivo Tomographic and Endoscopic Imaging of Experimental Orthotopic Colorectal Cancer
Wael Yared, Ph.D.,Vice President, Department of Imaging Systems, VisEn Medical, Inc.
The aim of this study was to detect colon cancer in an orthotopic tumor model using a fluorescent protease-activated near-infrared probe and multiple imaging modalities. CT-26 cells were implanted orthotopically into the colons of nude mice. Mice were injected with a CathepsinB-activated probe, imaged 24 hours later with a custom colonoscope, and with Fluorescence Molecular Tomography (FMT), a novel quantitative in vivo 3D imager. Results were corroborated by excision of the colons for ex vivo planar imaging and histology. We obtained in situ images and tumor fluorescence data with both endoscopy and FMT with a high tumor to background ratio and clear differentiation from the colons of control animals. Ex vivo imaging and histology confirmed the presence, localization, and size of tumors. Colorectal cancer can be imaged in vivo non-invasively with protease-activatable agents via endoscopy and 3D fluorescence tomography, validating the benefits of these new imaging modalities in cancer research.
6:00 End of Day Two of Imaging Week
