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Thursday, June 17
8:20 Chairperson's Remarks
Cornelia Reininger, M.D., Ph.D., Director, Global Clinical Development, Bayer Healthcare Pharmaceuticals
8:30 Imaging of Alzheimer’s Disease: A Drug Discovery and Development Perspective
Thomas Krucker, Ph.D., Head, Molecular Imaging, Global Imaging Group, Novartis Institutes for Biomedical Research, Inc. (NIBRI), USA
Genetically modified mice modeling Alzheimer’s disease enable the study of disease progression, determine early diagnosis, and test potential therapeutic interventions. Exploring new concepts and imaging strategies allowed us to successfully monitor non-invasively amyloid deposition, a hallmark of Alzheimer’s disease, using novel probe technology. Although challenging, translation of such strategies into clinical applications have great potential. Various approaches, possible alternatives and limitations will be discussed.
9:00 The Role of Amyloid Tracers in Disease Detection in AD, Early Identification and Pre-Selection for Therapy
Cornelia Reininger, M.D., Ph.D., Director, Global Clinical Development, Bayer Healthcare Pharmaceuticals
Disease modifying therapy in AD is most effective if applied before irreversible damage to brain tissue occurs. An imaging tool that detects cerebral ß-amyloid during life can facilitate early diagnosis and pre-selection of patients who will benefit from therapy. Beta-amyloid targeted imaging can also help decrease sample size, follow-up time and, thus, overall time and cost to development.
9:30 Pre-Clinical Imaging of Amyloid-BETA Plaque: In Search of an Animal Model
Cyrille Sur, Ph.D., Director, Imaging, Merck Research Laboratories
The deposition of amyloid-BETA (ABETA) plaque in the brain is a hallmark of Alzheimer's Disease (AD). Brain ABETA deposits can be imaged in AD patients with specific positron emission tomography tracers such as [11C]PIB and [18F]AV-45. Yet, ABETA plaque imaging in pre-clinical animal models has not been successful and I will present results from the evaluation of various technologies and animal models.
10:00 Networking Coffee Break, Poster and Exhibit Viewing
10:45 Challenges to the Application of Imaging to the Therapeutic Drug Development Pipeline
James Tatum, M.D., Associate Director, Division of Cancer Treatment and Diagnosis, NCI/NIH
The high expectation that “in vivo” imaging would play a pivotal enabling role in oncology therapeutic drug development has not been met. While there are rare examples of success, the wide-scale incorporation of advanced imaging into trials, especially those involving new targeted therapies, has not materialized. While there are more examples of success in the non-clinical area, “in vivo’ measurements of relevant biomarkers that can be translated have been elusive. When the significant additional cost of imaging is added, it is not difficult to appreciate the diminishing enthusiasm for advanced imaging in the drug development pipeline. So what went wrong? Was it an issue of unrealistic expectations or the inevitable result of hypothetical meeting reality? The answer is probably both. In this presentation, we will discuss the barriers and challenges that have led us to this point and the actions currently being taken by the National Cancer Institute to address these issues in an era were “in vivo” imaging will be pivotal to the implementation of personalized medicine for the oncology patient.
11:15 Target-Cell Specific "Smart" Imaging Probes for Super-Specific Cancer Cell Detection
Hisataka Kobayashi, M.D., Ph.D., Chief Scientist, Molecular Imaging Program, NCI/NIH
A major goal of targeted molecular imaging of cancer is to improve the sensitivity and specificity so that even minimal clusters of aberrant cells can be detected in vivo, thus permitting earlier intervention. Because the target―in this case a tumor―is only detectable in reference to its background, the most common strategies to improve imaging involve increasing the signal from the target tissue while assuming the background signal will remain constant. Herein, we propose several different fluorescence-based activatable “smart” strategies of maximizing target signal while minimizing or eliminating the background signal.
Sponsored by
11:45 pm Luncheon Presentation
In Vivo Biophotonic Imaging – Applications within the Cancer Setting
Christine L. Olsson, Ph.D. Commercialization Scientific Director, Taconic
Biophotonic imaging is a powerful phenotypic tool for dissecting physiological processes and evaluating compound efficacy in vivo. Here, we describe several orthotopic and metastatic paradigms in which this non-invasive modality may be used in combination with highly sensitive instrumentation to monitor longitudinal cancer progression and metastasis in the context of the same group of animals. Data and applications of various xenograft models will be presented.
12:15 pm Luncheon Presentation (Sponsorship Opportunities Available) or Lunch on Your Own
1:15 Chairperson's Remarks
Essa Hu, Ph.D., Principal Scientist, Medicinal Chemistry, Amgen
1:25 Using Imaging Techniques to Characterize Novel Histamine H3 Antagonists
Michael A. Letavic, Ph.D., Research Fellow, Neuroscience, Johnson & Johnson PRD, L.L.C.
Pre-clinical imaging techniques are extremely useful tools for discovery research, particularly in neuroscience where there are limited methods available for determining the drug levels required for target engagement. In this presentation we will discuss the application of several pre-clinical imaging techniques that were used to determine the extent of target engagement and duration of action of novel histamine H3 antagonists.
1:55 Molecular Imaging of Cancer: Prediction and Early Detection of Therapeutic Response
Jerry D. Glickson, Ph.D., Professor and Director, Molecular Imaging, Department of Radiology, University of Pennsylvania School of Medicine
The lecture will focus on NMR and optical imaging applications to cancer including: 1) Prediction and Early Detection of Therapeutic Response of Non-Hodgkin's Lymphoma by 31P and 1H MRS, 2) Detection of Response to mTOR Inhibitors by 1H MRS, and 3) Prediction of Metastatic Potential of Melanoma and Breast Cancer by Optical and MR Imaging.
2:25 Ice Cream Refreshment Break in the Exhibit Hall
3:05 in vivo Imaging after Non-Viral RNA Gene Delivery to the Brain
James Hecker, Ph.D., M.D., Assistant Professor, Anesthesia and Critical Care, University of Pennsylvania
CNS targets are of great interest, particularly with the discovery of siRNA and other small RNA regulatory sequences. However, delivery and expression in the CNS remains a problem. We describe formulations and methods for widespread delivery, uptake, biodistribution, and expression, as measured by in vivo imaging, of RNA lipoplexes.
3:35 From Small Molecules to Biologics and Nanoparticles—(Optical) Imaging Probe Designs for Pre-Clinical Applications and their Potential Translation
Rainer Kneuer, Ph.D., Research Investigator II, Lab Head, Tracer Development, Novartis Institutes for Biomedical Research, Inc.
The presentation describes the design, characterization and application of probes for a comprehensive optical imaging platform (fluorescence live cell microscopy, intravital microscopy, near-infrared fluorescence imaging) to selectively highlight physiological processes or molecular events relevant for drug discovery and development in vivo in small animals. Finally the translation of optical imaging tools to the clinical arena will be discussed.
4:05 EXPERT PANEL: Asking the Right Biological Questions—Tailoring the Imaging Solution
Using Imaging to monitor:
The distribution of a drug
Expression of a target
Drug at the site of target
Monitoring pharmaceutical readout
Panelists:
Stacey Oppenheimer, Ph.D., Senior Scientist, Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Pfizer, Inc.
James Hecker, Ph.D., M.D., Assistant Professor, Anesthesia and Critical Care, University of Pennsylvania
Michael A. Letavic, Ph.D., Research Fellow, Neuroscience, Johnson & Johnson PRD, L.L.C.
4:35 End of Conference
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