Day Two: Wednesday, November 17

7:30   Morning Coffee ( Technology Workshop Sponsorship Available)

8:25   Chairperson's Remarks
Derek Maclean, Ph.D.

Pre - Clinical Imaging

9:10   Non-Invasive Imaging of Adenovirus Transductional Retargeting and Transcriptional Restriction
Harvey R. Herschman, Ph.D., Ralph and Marjorie Crump Professor, Crump Institute for Molecular Imaging, Vice Chair, Molecular and Medical Pharmacology, UCLA 
Adenoviral vectors have a number of advantages in gene transfer protocols. However, their cellular trophism and tissue specificity can work against the therapist. We have used in vivo molecular imaging to monitor transductional "untargeting" of normal tissues and transductional "retargeting" to tumor cells that express large amounts of Epidermal Growth Factor receptors. We have also used in vivo molecular imaging techniques to demonstrate non-invasively selective expression of imaging/therapeutic genes to tumors that express elevated COX-2 levels, with concommitant restricted expression 
in tissue. 

9:40   Detection of Tumors and Metastasis in Live Animals With Bacteria and Vaccinia Virus Encoding Light-Emitting Proteins
Aladar A. Szalay, Ph.D., Professor, Virchow Center for Experimental Biomedicine and Institute for Microbiology, Biocenter, University of Wurzburg, President and CEO, Genelux Corporation
During the past two years, we have shown that bacteria injected intravenously to live rodents with tumors entered and replicated in solid tumors and metastases. The tumor-specific amplification process was visualized in real time using luciferase-catalyzed luminescence and green fluorescent protein fluorescence which revealed the location of the tumors and metastases. Bacterial strains, E.coli, and three attenuated pathogens (Vibrio cholerae, Salmonella typhimurium, and Listeria monocytogenes) all entered and replicated within the tumors. In addition to bacteria, the cytosolic vaccinia virus also showed tumor-specific replication as visualized by real-time imaging. The findings presented in this paper indicate that neither auxotrophic mutations nor specific mutations in the viral genome were required for tumor specificity and replication in the tumor tissue. We also observed localization of tumors by light-emitting microorganisms in both immunocompetent and in immunocompromised animals with syngeneic and allogeneic tumors. Further, the potential of visualization of tumor regression based on light extinction in the tumor tissue will also be discussed. Based on their tumor-finding nature, bacteria and viruses may be designed to carry multiple genes for the simultaneous detection and treatment of cancer.

10:10   Coffee Break, Poster and Exhibit Viewing (last chance)

10:50   Tumor Target Discovery and Validation through Integration of Subtractive Proteomics and Molecular Imaging In Vivo
Jan E. Schnitzer, M.D., Scientific Director, Professor of Cellular & Molecular Biology, Director of Vascular Biology & Angiogenesis Program, Sidney Kimmel Cancer Center
Tissue molecular complexity and in vivo inaccessibility of cells within tissue restrict target discovery for tissue-specific imaging and pharmacodelivery. A new systems biology approach that integrates subcellular fractionation, subtractive proteomics, bioinformatics and molecular imaging is used to identify and quickly validate key tissue-specific proteins induced at the tissue-blood interface and inherently accessible to agents injected intravenously. Immunotargeting and tissue penetration of single organs and solid tumors occurs in <1 hour and targeted radio-immunotherapy destroys tumors. Mapping tissue- and disease-modulated endothelial cell surface and caveolar proteins reveal promising targets for molecular imaging and therapy.

11:20   In Vivo Biophotonic Imaging: Application in Oncology and Gene Expression
Anthony F. Purchio, Vice President and Chief Scientific Officer, Xenogen Corporation
Xenogen's technology is based on the detection and quantification of light transmitted through living mammalian tissue. Microorganisms such as tumor cells are tagged with a luciferase gene and their growth is non-invasively monitored via photon counting over time. Gene expression in living transgenic animals can be monitored by using specific promoters of interest to drive luciferase. Several applications in the field of oncology and gene expression will be presented. The applications for drug discovery in these areas will be highlighted.

11:50   Lunch on Your Own ( Technology Workshop sponsorship available)

1:25   Chairperson's Remarks
Aladar A. Szalay, Ph.D.

1:30   In Vivo Imaging of Protease Activity via Small Molecule Probes
Amos Baruch, Ph.D., Senior Scientist, Chemical Proteomics, Celera Genomics 
We have developed a chemical proteomics approach that utilizes a unique set of activity-based probes for determining enzymatic activity in vivo. Using such biochemical tools directed against the papain-family of cysteine proteases, we were able to identify key-proteases that play a role during the initiation and progression of pancreatic islet cells cancer in the RIP-TAG transgenic model. Fluorochrome-tagged activity-based probe allowed the imaging of enzyme activity within the tumor. Activity-based in situ imaging in combination with biochemical analysis revealed that most of the protease activity within the tumor is contributed by inflammatory cells. These experiments represent the utilization of novel imaging and biochemical reagents and provide an additional step towards understanding the role of cysteine proteases in cancer. In collaboration with Johanna Joyce, Douglas Hanahan, Department of Biochemistry, UCSF and Matthew Bogyo, Department of Pathology, Stanford University Medical School.

2:00   In Vivo Fluorescent Imaging in Zebrafish
Nikolaus S. Trede, M.D., Ph.D., Dept. of Hematology, Children's Hospital, Harvard Medical School
Zebrafish are an important vertebrate genetic and developmental model system because of their optic transparency, rapid development, prolific fecundity and ease of mutagenesis. Lineage-tracing using fluorochromes has been a powerful tool that facilitates in vivo observation of developmental processes and screening of mutants. However, background fluorescence from surrounding tissues can impede interpretation of results. We have generated a transgenic line of zebrafish where GFP is expressed exclusively in T cells. Using a tunable imaging filter we were able to distinguish even weak GFP signals from background in embryos and adult zebrafish.

2:30   Refreshment Break

Clinical Applications

2:45   Molecular Imaging in the Assessment of Molecular-Targeted Therapies: Clinical Applications
Annick D. Van den Abbeele, M.D., Acting Clinical Director, Department of Radiology and Director, Division of Nuclear Medicine, Dana-Farber Cancer Institute, Associate Professor of Radiology, Harvard Medical School
Molecular targeting of specific dysregulated enzymatic pathways has great promise for developing a new generation of less toxic and more effective anticancer therapies. With these new drugs, certain biologic effects might become evident very early in the course of therapy, before the evolution of significant morphologic changes detectable by conventional anatomic imaging. Since cellular uptake and retention of the glucose analog FDG is a common phenomenon in many cancers, a functional imaging modality such as PET imaging may provide a way to detect metabolic changes within tumors very early on following initiation of molecularly targeted anticancer therapy. Data from our collaborative study team provide promising support for this hypothesis. A review of these data will be presented.

3:15   Prospect of Molecular Imaging in Humans 
Johannes Czernin, M.D., Professor, Chief, Ahmanson Biological Imaging Division, Molecular and Medical Pharmacology, University of California, Los Angeles
The field of molecular imaging is rapidly expanding. Its goal in humans is to provide an array of imaging probes and technologies that target specific molecular processes characteristic for individual cancers. This would not only allow for better diagnosis and staging but also for improved treatment monitoring. The advances in molecular imaging have been facilitated by discoveries in tumor biology as well as by advances in drug and technology development. Important new signal transduction pathways and their alterations have been uncovered in recent years leading to novel and exciting treatment strategies. The effects of such treatments can be evaluated with surrogate markers of disease and disease responses such as, among others, the glucose analogue18 F-fluorodeoxyglucose (FDG) or the thymidine analogue 18F-fluorothymidine (FLT), or the amono-acid analogue 18FDOPA. Thus, molecular imaging benefits the drug evaluation process by providing a unique tool for measuring treatment responses in vivo. In addition, therapeutic drugs can be labeled with positron emitting isotopes and might thus be useful to predict their bio-distribution, pharmacokinetics and pharmacodyamics in vivo. Utilizing these approaches requires an interdisciplinary collaboration between tumor biologists, experts in the field of molecular imaging, physicists, mathematicians, physicians, and leaders in the pharmaceutical industry. Together, this diverse group of scientists is shaping the field of molecular imaging. The emphasis of this presentation is laid on those imaging probes that might be relevant for clinical use in cancer patients. Some of the described probes are clinically established while others are in early stages of preclinical or clinical evaluation.

3:45   Panel Discussion with Speakers

4:15   End of Conference