TUESDAY, NOVEMBER 18
8:00 Registration and Morning Coffee
Emerging Probes and Marker Developments
8:30am Chairperson’s Remarks
8:35 in vivo Targeted Imaging Using MR Signal Amplification Probes
Alexei Bogdanov, Jr., Ph.D., Professor, Radiology, Cell Biology, University of Massachusetts Medical School
Small molecular mass paramagnetic probes with enzymatic specificity were designed for imaging of expression of disease specific markers using the relaxivity increase effect due to polymerization and retention in vivo effect. We applied the MR amplification strategy for imaging inflammation-specific endogenous enzymes and imaged receptors using targeted enzyme-tagged agents. The MR imaging at high spatial resolution enabled imaging EGFR expression on the surface of tumor cells in vivo and experimental inflammation in vascular wall. This technique can be potentially translated into the clinical practice since they are similar to currently approved contrast agents.
9:05 The Imaging Probe Development Center at the National Institutes of Health
Gary Griffiths, Ph.D., Director, Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health
The IPDC at NIH has been set up for the production and supply of known and novel imaging probes for use in any imaging modality including optical, radionuclide, ultrasound and magnetic resonance agents. IPDC has now been at near-full operation for just over one year during which time it has worked with over thirty principal investigators from within the NIH intramural research community, producing a variety of molecular imaging probes for their research. Examples of probes already prepared or under preparation will be described. Going forward, it is planned that IPDC can offer its synthetic, radiochemistry and bioconjugate chemistry services to extramural scientists, particularly to those imaging scientists who may be limited by their lack of chemistry support.
9:35 Technology Showcase: Novel Bioluminescent Imaging Substrates
Dieter Klaubert, Ph.D., Director, Research and Development, Promega Biosciences
Although luciferin has been used extensively for imaging in mice, examples of substrates that can image more specific biological processes have recently become available. Modifications of luciferins, the proluciferins, can be used to alter the tissue distribution and the pharmacokinetics in mice, and most importantly, they can be used to image specific enzyme activity in the whole animal. We have modified luciferins and coelenterazines for a variety of enzymes, some of which have demonstrated utility in in vivo imaging applications. Many more have potential for this application, and their in vitro activity will be presented.
10:05 Networking Coffee Break, Exhibit and Poster Viewing
10:45 Bimolecular Fluorescence Complementation and its use In Studying Signal Transduction Networks
John O’Bryan, Ph.D., Assistant Professor, Pharmacology, University of Illinois at Chicago
The assembly of signal transduction complexes, or signalosomes, and the regulation of these complexes in time and space represents an intense area of research investigation. Bimolecular fluorescence complementation (BiFC) represents a novel fluorescent approach to study the assembly of signaling complexes in living cells. We will discuss our results using this method to probe the function of a novel scaffolding protein involved in coordinating endocytosis, ubiquitylation, and cell survival pathways.
11:15 Proteomic Imaging of Vascular and Caveolar Targets in vivo: Probes that Penetrate into Single Organs and Solid Tumors
Jan E. Schnitzer, M.D., Scientific Director, Professor, Cellular & Molecular Biology; Director, Vascular Biology & Angiogenesis Program, Sidney Kimmel Cancer Center
Current noninvasive molecular and functional imaging as well as pharmacodelivery by targeting disease biomarkers is challenged by in vivo barriers limiting access. Epithelium and endothelium prevent tissue penetration of many imaging agents, drugs, nanoparticles and gene vectors. Our discovery and validation strategies integrate tissue subfractionation, subtractive proteomics, bioinformatic interrogation, antibody generation, expression profiling, and various imaging modalities to identify quickly the in vivo targetable subset of biomarkers. Mapping proteins in caveolae at endothelial cell surfaces yield novel vascular biomarkers enabling not only tissue- and disease-specific immunotargeting in vivo but also penetration into the tissue. This “organellar proteomic imaging of organ and disease biomarker space” creates opportunities for imaging physiological and pathological functions in vivo as well as treating many diseases.
11:45 Panel Discussion: The Optimal Probe – Future or Fantasy?
12:15pm Lunch on Your Own or Luncheon Workshop
(Sponsorship Available)
Imaging Modalities
1:40 Chairperson’s Remarks
1:45 The Molecular Biology and Genetics of Transgenic Fluorescent Mice for in vivo Imaging
James Denegre, Ph.D., Associate Research Scientist, Light Microscopy and Cytogenetics, The Jackson Laboratory
Mouse models of disease have become the primary tool for translational research, driven in part by the ability to make transgenic mice expressing specific fluorescent molecular markers. However, the final reagent is a live mouse with a complex biology, presenting unique challenges and opportunities. Advances in fluorochrome generation and genetic technology allows for the creation of a diverse, sophisticated toolbox for in vivo imaging. To enable the investigator to get the most out of their mouse we discuss the molecular biology of transgene
construction, the genetics of transgene behavior and the genetic manipulations available to drive temporal and cell- specific expression, and the resultant biology of the mouse.
2:15 Finding Things in Mice: Dynamic Contrast Enhancement and Machine-Learning Image Segmentation
Richard M. Levenson, M.D., Vice President, CRI
Obtaining high-quality images is a necessary but not sufficient component in the overall task of extracting quantitative information from in-vivo animal models. CRI has developed an automated image segmentation capability (a teachable similarity engine) that uses “learn-by-example” methods to create a multi-class classifier. While its feature selection and neural-net-based learning procedure are sophisticated, the complexities are hidden from the user. Errors in classification are corrected by amending the training regions, and then repeating the training and classification steps. Depending on the image size, the entire training process can take from just seconds to minutes, and the resulting classifier can be used to segment additional images as part of an automated analysis suite. Classification accuracy seems excellent across a wide variety of imaging modalities, including X-ray, CT, MR, ultrasound, OCT and various forms of optical imaging, including DyCE(tm), and at a variety of scales from whole animal to the microscopic.
2:45 Optical Imaging of Bacterial Infection in Living Animals
Bradley Smith, Ph.D., Emil T. Hofman Professor of Chemistry and Biochemistry; Director of the Notre Dame Integrated Imaging Facility, Chemsitry and Biochemistry, University of Notre Dame
Recent advances in optical imaging of bacterial infection have been propelled by the invention of genetic methods that produce fluorescent and bioluminescent bacteria, and also the discovery of synthetic fluorescent probes that selectively target bacterial cell surfaces. Optical imaging is an effective method for conducting longitudinal studies of bacterial infection in small animals. It can be used to address questions in medical microbiology concerning migration and colonization and it is an attractive method for determining the efficacy of antibiotic therapies.
3:15 Networking Refreshment Break in the Exhibit Hall
4:00 Optoacoustics for Molecular Imaging
Robert Lemor, Ph.D., Division Director, Ultrasound, Fraunhofer Institute for Biomedical Engineering IBMT
Optoacoustic imaging is a new promising modality in biomedical imaging integrating the benefits of optics and ultrasound. When biological tissue is irradiated with ultrashort laserpulses of durations of a few nanoseconds, the light is absorbed according to the local absorption properties in the tissue, and is converted successively into heat and pressure by means of the thermoelastic effect. The generated pressure can be detected and visualized for diagnostic purposes with similar techniques as in pure ultrasound imaging. Beside the advantage of imaging optical contrast with deep penetration and high resolution, the modality also allows for the use of contrast agents. For contrast enhanced imaging, different types of targeted nanoparticles can be used. The technology and possible applications as well as first results on the suitability of different types of contrast agents for optoacoustic in vivo imaging will be discussed and an outlook will be given.
4:30 Applications of fMRI in Drug Discovery and Development: Aβ1-40 Induced Changes in Cerebral Perfusion in Mice
Gerard B. Fox, Ph.D., Head, Imaging, Experimental Imaging, Abbott Laboratories, USA and CNS Discovery Research, Abbott Laboratories, Germany
Neurovascular regulation, which is critical to the efficient functioning of the brain, is impaired in Alzheimer's disease and in transgenic mice overexpressing Abeta. Although senile plaques and neurofibrillary tangles represent neuropathological hallmarks of Alzheimer's disease, soluble Abeta, which shows greater correlation with disease progression and severity, displays strong vasoactive properties. This presentation will focus on a non-invasive model of cerebral vasoactivity utilizing fMRI, which will ultimately be translatable to Alzheimer's disease as a marker for disease-modifying efficacy of novel small molecules and biologics drugs.
5:00 End of Day Two
Day 3