Sessions Include:• Novel Probes and Techniques

• Assay Development

• Real Time Imaging

• Optical Imaging

• Bioluminescence

Presenting Companies:• AntiCancer, Inc.

• Los Alamos National Laboratory

• Merck & Co., Inc.

• National Institutes of Health

• Novartis Pharmaceuticals Corporation

...and more!

Sessions Include:• Bioluminescence

• Preclinical Imaging

• Imaging in- Neurology

- Cardiology

- Oncology

Presenting Companies:• Boehringer Ingelheim Pharma GmbH & Co.

• GlaxoSmithKline, UK

• Harvard Medical School

• Kodak Molecular Imaging Systems

• Pfizer, Inc.

...and more!

Third Annual

Fluorescent Proteinsin Drug DevelopmentNovember 13-14, 2006Hilton La Jolla Torrey Pines • La Jolla, CA

Third Annual

In Vivo Molecular ImagingMoving from Discovery to Preclinical to Clinical Applications

November 14-15, 2006Hilton La Jolla Torrey Pines • La Jolla, CA

Cambridge Healthtech Institute250 First Avenue, Suite 300, Needham, Massachusetts 02494 • T: 781-972-5400 or toll-free in the U.S. 888-999-6288 • F: 781-972-5425 • www.healthtech.com

Corporate Sponsors:

Final AgendaC

am

brid

ge

He

alth

tec

h In

stitu

te P

rese

nts:

www.imaging-week.com

Executive Sponsor:

Register by September 1st

and Save up to

$350!

Sponsoring Associations:

www.imaging-week.com 2

Fluorescent Proteins in Drug DevelopmentSunday, November 12

5:00-6:00 pm Early Registration

Monday, November 137:00 am Registration and Morning Coffee

Novel Fluorescent Probes and Techniques7:50 Chairperson’s Opening RemarksAndrew Bradbury, Ph.D., Staff Scientist, Biosciences Division, Los Alamos NationalLaboratory

8:00 The Creation of a Novel Fluorescent Protein by GuidedConsensus Engineering

Andrew Bradbury, Ph.D., Staff Scientist, Biosciences Division, Los Alamos National LaboratoryWe have created a novel fluorescent protein based on the consensus derived from the alignment of31 fluorescent proteins. This consensus protein is extremely well expressed, monomeric and fluores-cent with red shifted absorption and emission characteristics compared to GFP. Recent data on thecharacterization of this novel fluorescent protein will be presented.

8:30 RNA Visualization in Live Bacterial Cells Using FluorescentProtein Complementation

Natalia Broude, Ph.D., Research Associate Professor, Center for Advanced Biotechnology andDepartment of Biomedical Engineering, Boston University We developed a new fluorescent imaging technique with very low background signal for studyingRNA dynamics in vivo. Using this technology, we observed synchronous spatial and temporalchanges of fluorescence in single bacterial cells. Our approach presents a substantial advance for cel-lular imaging since it adds fluorescent protein complementation to the existing arsenal of methodsfor RNA labeling in vivo.

9:00 Optimized GFP Fragment Complementation Assays forProtein Tagging and Detection

Geoffrey S. Waldo, Ph.D., Bioscience Division, Los Alamos National LaboratoryWe describe the properties and applications of self-assembling GFP fragments for monitoring pro-tein expression in vivo and in vitro, and for 'discovering' compact protein domains that are suitablefor downstream applications. These fragments can also be used for monitoring the assembly of multi-protein complexes and for high-throughput protein expression assays.

9:30 Use of Kaede Fusions to Visualize Recycling andDegradation of G Protein - Coupled Receptors

Dr. Antje Schmidt, Staff Scientist, Leibniz Institute of Molecular PharmacologyG protein-coupled receptors (GPCRs) represent important drug targets. Trafficking of GPCRs hasbeen widely studied using fusions with green fluorescent protein (GFP) derivatives. For many exper-iments, however, marker proteins would be desirable whose fluorescence can be converted once theprotein has reached a particular membrane compartment. Here we show that fusions with the Kaedeprotein from the coral Trachyphylla geoffroy may be useful to fill this gap. Kaede emits green fluo-rescence that can be irreversibly converted to red using UV light (364 nm). With the help of C-terminal Kaede fusions and confocal laser scanning microscopy, we have established a novelmethodology to study GPCR recycling and degradation: Initially, receptors at the plasma membraneare internalized using agonists. The fluorescence is then switched from green to red. Thereafter, traf-ficking of the receptors to target compartments such as the plasma membrane or lysosomes can beeasily visualised by monitoring their new fluorescence.

10:00 Networking Coffee Break

10:30 Exploiting the Convergence of Fluorescence Imaging,Cellular Networks, and Chemical Biology

John K. Westwick, Ph.D., President and CSO, Odyssey Thera, Inc.Biological responses to drugs are determined by the architecture and dynamics of the cellular signaltransduction network. We are using massively parallel arrays of high content, fluorescence-basedassays, including Protein-fragment Complementation Assays (PCA), to perform live cell, pathway-based drug discovery and drug profiling. Our approach enables assessment of “un-drugable” targets,and identification of on-target and off-target effects of lead compounds at an early stage in the dis-covery process.

11:00 Solutions Showcase:Correlating Cellular Imaging with Protein Interactions Using the HaloTag Technology

Randy Learish, Senior Scientist, R & D, Promega CorporationOften it is desirable to associate imaging data gained through fluorescence microscopy with bio-chemical analyses of the subcellular components. HaloTag fusion proteins can be labeled withincells by a variety of fluorophores and captured from the cells as protein complexes through covalentlinkage to HaloLink surfaces. An example will be given showing correlative analysis of p65 biology.

11:15 Solutions ShowcaseGet informed on the newest technology and developments. Contact Carol Dinerstein at 781-972-5471 for sponsorship opportunities.

11:30 Novel Fluorescent Probes to Measure and Manipulate thep53 Pathway

Kenneth Giuliano, Ph.D., Principal Scientist, Research and Development, Cellumen, Inc.The p53 tumor suppressor pathway contains potential drug targets, such as the ubiquitin ligaseHDM2, that are difficult to screen with conventional high content screening (HCS) methods. Wehave generated tools to manipulate expression of an HDM2-GFP fusion protein with a tightly-reg-ulated promoter system, and to measure the interaction of p53 and HDM2 with a new fluorescent-protein-based protein:protein interaction positional biosensor. Multiplexed HCS are used to simul-taneously monitor several aspects of p53 pathway activity, including cell cycle regulation, organellefunction, DNA damage response, and apoptosis. These tools facilitate a new systems cell biologyapproach to studying pathway activity that enables drug discovery for novel target classes.

12:00 Panel Discussion with Speakers

12:30 Lunch on your own (Luncheon Workshop Sponsorship Available)

Assay Development2:00 Fluorescent Protein Assays Using 1536-Well-Plate-Based

Laser-Scanning Microplate Cytometry and qHTSDoug Auld, Ph.D., Group Leader Genomic Assay Technologies, NIH Chemical GenomicsCenter, National Human Genome Research Institute, National Institutes of HealthThe National Institute of Health Chemical Genomics Center (NCGC) has developed a processtermed “quantitative HTS” (qHTS) where > 70,000 compounds are screened as concentration-titration series in a high-throughput mode. The process has been applied to a variety of fluorescentprotein - based assays utilizing the Acumen Explorer laser plate cytometer. This talk will focus oncase studies covering a wide range of biology that has been successfully applied using microplatecytometry at the NCGC. Specifically, the ability to measure cytoplasmic to nuclear translocationusing cells expressing fluorescent protein fusions (BioImage cell lines, Promega’s HaloTag technol-ogy), and the use of bifurcated FPs (Odyssey Thera) will be illustrated.

2:30 A FRET Cell-Based Assay for Insulin - Receptor ActivationShane Marine, Ph.D., Department of Automated Biotechnology, Merck & Co., Inc.

3:00 A Novel Generic High Throughput System for Kinase AssaysJun Wu, M.D., Ph.D., Product Manager, Biochemical Assays, Nanostream Inc.Protein kinases control many cellular activities through protein phosphorylation and dephosphoryla-tion in response to extra cellular signals. Abnormality in the activities of the kinases in these regula-tion pathways have been linked to many human diseases. Classical screening platforms, e.g., radioac-tive methods and ELISA-based assay methods, generally require multiple labor-intensive and time-consuming steps. To address these kinase assay limitations, we have developed a generic high-through-put screening assay. In this assay, nonphosphorylated peptide was used as a substrate., The phosphory-lated peptide was resolved from nonphosphorylated peptide via micro parallel chromatography. Incontrast to a traditional plate reader based kinase assay, the Nanostream LD system could detect lessthan 10% conversion of enzymatic reactions and Z’ factor ranges from 0.6 to 0.85. In addition, this sys-tem can enable real time monitoring of kinase kinetics. From a single experiment, the optimal enzyme,ATP, and substrate concentrations can be determined. Furthermore, the collected data allows Kmdetermination for ATP and substrate and for time course study. Compared with conventional HPLCand LC-MS, our system enables parallel chromatographic analysis of 24 samples. The system is simpleto use, and the integrated system software permits fast and accurate data analysis. The system can beused to facilitate target identification and assay development in drug discovery.

3:30 Refreshment Break, Poster and Exhibit Viewing

4:15 Optical Imaging for Anti-Cancer Drug Discovery andDevelopment

Wafik El-Deiry, M.D., Ph.D., Professor, Department of Medicine, Genetics, Pharmacology,University of Pennsylvania School of MedicineIn the last several years we have developed the infrastructure and have performed high through-putcell-based screening using optical imaging including bioluminescence as a read-out to identify can-didate therapeutic agents. Target validation and anti-tumor effects have been demonstrated. Wehave also been developing various strategies to image drug effects in vivo including assays of apop-tosis and gene expression changes using molecular beacons or Q-dot labeled probes. We are movingin the direction of using medicinal chemistry and genomic approaches to continue to discover anddevelop novel anti-cancer drugs as well as imaging probes. Optical imaging provides a powerful toolfor screening, target validation, and in vivo studies of anti-tumor effects. The NCI-funded Networkfor translational research in Optical Imaging has supported these efforts.

Real-Time Imaging4:45 Whole-Body Subcellular Imaging in the Live MouseRobert M. Hoffman, Ph.D., President, AntiCancer, Inc.Dual-color cancer cells expressing GFP in the nucleus and RFP in the cytoplasm have been devel-oped. These cells enable nuclear-cytoplasmic dynamics, cell cycle analysis, apoptosis, nuclear andcytoplasmic shape changes, and numerous other processes to be visualized in the living mouse. TheOlympus IV100 whole-mouse laser-scanning microscope with ultra-thin diameter objectives enablethe dual-color cells to be visualized external to the mouse. Using host mouse models expressing GFPin all cells enables for the first time the study of tumor-host interaction at the cellular level in realtime. This technology will lead to the development of the new field of in vivo cell biology to studyboth normal and disease processes in the live animal at the subcellular level.

5:15 Panel Discussion with Speakers

5:45 Networking Reception in Exhibit Hall

6:45 End of Day One of Imaging Week

Sponsored by

November 13

Photo Credit: Mouse Image Courtesy of CRI, Inc.

www.imaging-week.com 3

Tuesday, November 147:15 Registration and Morning Coffee

(Sponsorship for Breakfast Workshop Available)

8:25 Chairperson’s Opening RemarksRichard Levenson, M.D., Director of Research, Biomedical Systems, CRI, Inc.

Optical Imaging9:15 In Vivo Optical Imaging Enabled by Soft-Matter Analogues of

the Quantum DotsMichael Therien, Ph.D., Professor of Chemistry, University of PennsylvaniaFormed through cooperative self-assembly of amphiphilic diblock copolymers and electronicallyconjugated porphyrinic near infrared (NIR) fluorophores, NIR-emissive polymersomes (50 nm - 50um polymer vesicles) define a family of organic-based, soft matter quantum dot analogues that areideally suited for in vivo optical imaging. We show that membrane incorporation of a wide range ofrelated multi-porphyrinic fluorophores enables emission energy modulation over a broad domain ofthe visible and near infrared spectrum (600-950 nm). Long-wavelength optical excitation of suchassemblies generates intense, highly localized, emissive signals capable of penetrating through thedense tumor tissue of live animals. New nanoscale polymersomal vesicles in which the componentamphiphilic diblock polymers are derived from two previously FDA-approved building blocks havebeen delineated, providing for fully bioresorbable probes. Excited-state transient dynamical studiesprovide insights into how NIR-emissive polymersomes can be further optimized for in vivo deep-tis-sue fluorescence-based imaging.

Bioluminescence9:45 Combining Bioluminescent Reporters and Fluorescent Probes for

Studying Tumor Growth and Biology in Mouse Xenograft StudiesSteven 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 inxenograft 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 oftumor 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 mole-cules 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 allowsthe 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 Responseto 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 pro-vide clinical benefit remains a dark art. Bioluminescence imaging (BLI) sheds light on active agentsand may predict FLT-PET responses. Correlative studies were conducted using BLI and FLT-PETimaging in xenografts used to evaluate novel combination therapies.

11:30 TBAKohkan Shamsi M.D., Ph.D., President, Symbiotic Pharma Research

Preclinical Imaging12:00 In Vivo Cellular MRI: Tracking Magnetically Labeled Cells in

Disease ModelsJoseph Frank, M.D., Chief, Experimental Neuroimaging Section, National Institutes of HealthMammalian stem cells or other cells are being considered for infusion or transplantation into tissuefor purposes of repair, regeneration or other therapeutic approaches. Cellular Imaging is a valuabletool for monitoring cell migration and trafficking in vivo. Magnetic labeling of cells provides the abil-ity to monitor their temporal spatial migration in vivo cellular MRI. The techniques for labeling cellswith MRI contrast agents have been well established in experimental systems and are presently beingtranslated to the clinic. In this presentation, I will describe the different approaches used to label cellswith 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 forthe evaluation of cellular based treatment effects in disease models.

1:55 Chairperson’s Remarks

2:00 In Vivo Preclinical Imaging in Drug DiscoveryMatthew Silva, Ph.D., Scientist, Imaging Science, Millennium Pharmaceuticals, Inc.The generally accepted role for medical imaging in preclinical pharmaceutical drug discovery anddevelopment is to assist in the advancement of animal disease models and to provide additional drugefficacy read-outs. The successful implementation of this strategy requires (1) the full commitmentof the institution to support the imaging group and (2) the keen ability of imaging scientists to iden-tify impact projects. This talk focuses on the integration of a multi-modal, small animal, in vivoimaging facility into the drug development process-including project prioritization, “pharmaceuti-cal-grade” throughput, assay robustness, and drug efficacy measurements.

2:30 Imaging Wortmannin: New Sights For an Old MoleculeLee Josephson, Ph.D., Associate Professor, Center for Molecular Imaging Research, HarvardMedical SchoolThe ability to image the fate of natural products in biological systems can provide valuable informa-tion about their behavior, and further development of drug leads based on this important source ofmaterials for pharmaceutical development. Fluorescent forms of wortmannin, a natural productinhibitor of PI3 Kinase, provide insights into the mechanism of wortmannin action and develop-ment of wortmannin based inhibitors of this enzyme, which plays an important role in controllingcell proliferation. In collaboration with Katie Barnes, Hushan Yuan, and Ralph Weissleder.

3:00 In Vivo Molecular Imaging of Spatio-Temporal DrugDistribution Using the Sub-Millimeter NanoSPECT/CT

Jeffrey P. Norenberg, MS, PharmD, BCNP, FASHP, FAPhA, Executive Director, NationalAssociation of Nuclear Pharmacies, Associate Director, New Mexico Center for Isotopes inMedicine, 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-headedNanoSPECT/CT system including discussions of resolution, sensitivity and uptake quantificationcapabilities. We will present results of initial pharmacokinetic studies performed with theNanoSPECT demonstrating the new-found strength of temporal imaging with multi-pinholeSPECT.

3:15 Solutions Showcase Get informed on the newest technology and developments. Contact Carol Dinerstein at 781-972-5471 for sponsorship opportunities.

3:30 Refreshment Break in the Exhibit Hall

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 GroupWilliam E. McLaughlin, Director of R&D, Kodak Molecular Imaging SystemsExciting new molecular imaging agents enable highly specific fluorescent, luminescent, andradioisotope imaging of disease processes within living animals. These in vivo molecular imagingagents provide the potential for rapid detection of specific changes within the target tissues longbefore morphological changes from disease or from disease treatment are present. Use of theseimaging agents in live animals has stimulated the development of multi-modal image systems,the application of which will be presented.

Sponsored by

Keynote Presentation

8:30 Molecular Imaging: From Research through DrugDiscovery to the Clinic-Defining Path Forward

Peter Lassota, Ph.D., Vice President, Oncology, Caliper Life Sciences

Fluorescent Proteins in Drug Development&

In Vivo Molecular ImagingNovember 14

For reservations, please call the hotel directly to make your arrangements. Identify yourself asa Cambridge Healthtech Institute conference attendee to receive the reduced room rate.

Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Hilton La Jolla Torrey Pines 10950 N. Torrey Pines Road • La Jolla, CA 92037 Tel: 858-558-1500 Fax: 858-450-4584CHI Discounted Room Rate: $189 s/d Discounted Reservation Cutoff:October 23, 2006

Conference & Hotel Venue

www.imaging-week.com 4

Wednesday, November 15

8:25 Chairperson’s Remarks

Imaging in Neurology9:15 Development of New Probes and Techniques for Optical

Imaging in Alzheimer’s DiseaseBrian Bacskai, Ph.D., Assistant Professor, Department of Neurology, Massachusetts GeneralHospital/Harvard UniversityAlzheimer’s disease is characterized by the progressive accumulation of senile plaques. An imag-ing technique sensitive to amyloid-beta accumulation in the brain would allow early diagnosisand effective drug screening with longitudinal monitoring. Recent success with radioligands forPET imaging are encouraging, but the expense and limited availability hinder widespread imag-ing. Similarly, microPET in animal models with current PET ligands do not seem to work. Anoptical approach for non-invasive imaging in animals, and ultimately humans, would be rela-tively inexpensive and widely available. Our goals are to develop novel small molecule contrastagents that are near infrared fluorescent, cross blood-brain barrier, and target Abeta specifical-ly. In combination, we are developing novel optical tomographic approaches to detect theseagents with high sensitivity and high spatial resolution in living animals. With an orchestrat-ed multidisciplinary approach, we expect to facilitate in vivo drug testing in animal models, andperhaps diagnose early stage Alzheimer’s disease in humans.

9:45 Strategies for Rapid Human CNS Biomarker Developmentand Application

John Seibyl, M.D., Senior Scientist, Nuclear Imaging, Molecular NeuroimagingThe purpose of this talk is to describe new vertically integrated models of CNS biomarkerdevelopment and implementation in human drug development trials using PET and SPECT.This describes focused primate screening methods, strategies for optimizing quanitative out-come measures, and large-scale implementation in Phase IIb- IV clinical trials in multicenterimaging settings with incorporation of Good Imaging Practices (GIP) and harmonization ofimaging across different cameras.

10:15 Coffee Break in Exhibit Hall

11:00 Multimodality Imaging of Alzheimer’s Disease: From Mouse to ManThomas Krucker, Ph.D., Head Molecular Imaging, Discovery Technologies, Novartis Institutesfor BioMedical Research, Inc. (NIBRI) Alzheimer’s disease (AD) is a neurodegenerative dementia characterized by neuronal loss, amy-loid deposition, and neurofibrillary tangles. Clinically, the most notable feature is a character-istic cognitive impairment. Vascular factors have been associated with the development ofmulti-infarct dementia, and might also be implicated in the pathogenesis of the disease. Despitedecades of intense research, there are no cures for AD. However, it has accelerated the insightsinto the biology of the disease and provided new aspects of the molecular underpinnings,including vast information about the genetics and associated risk factors. We are using differ-ent lines of mutant mice modeling Alzheimer’s disease to study disease progression, determineearly diagnosis, and test potential therapeutic interventions. Exploring new concepts and imag-ing strategies allowed us to visualize vascular alterations and changes in blood flow at earlystages of the disease. In addition, we now can successfully monitor non-invasively amyloid dep-osition, a hallmark of Alzheimer’s disease, using novel probe technology. Although challeng-ing, translation of such strategies into clinical applications have great potential. First attemptsand possible alternatives will be discussed.

Keynote Presentation8:30 Target-cell Specific in vivo Molecular Imaging of Cancer

using Multicolor Activatable Fluorescence ProbesHisataka Kobayashi, M.D., Ph.D., Chief Staff Scientist, Molecular ImagingProgram/Center for Cancer Research/National Cancer Institute/NIH

7:45 am Breakfast Workshop

The Simultaneous Measurement of Blood Flow and Biochemistry via Optical Imaging

David R. Vera, Ph.D., Professor, Moores UCSD Cancer Center, University of California, San DiegoImaging via time domain optical imaging provides a unique opportunity to simultaneouslymeasure multiple biochemical and or physiologic parameters. There are two features of timedomain (TD) methodology that enable the multiple measurements. First, TD permits imagereconstruction, which provides correction for depth-effects. This correction properly pre-pares the imaging data for kinetic modeling, which can be employed to measure multipleparameters. Second, TD-based optical imaging offers the opportunity to inject multipleprobes with differing optical lifetimes. This strategy, for example, would permit the simulta-neous injection of two probes: one to measure blood flow and the other to measure a bio-chemical marker, such as receptor density or affinity. Examples will be provided for this strat-egy, as well as, the use of kinetic modeling. These methods, and consequently the need fortime-domain imaging, will be required to properly interpret preclinical imaging for drugdevelopment, where a constant problem is the separation of delivery and biochemistry. Forexample, if an optical image of a tumor has decreased in fluorescence intensity after a ther-apy protocol, was the decreased uptake by the probe due to decreased tumor blood flow or adecrease in the density of the biochemical marker within the tumor?

Sponsored by

In Vivo Molecular ImagingNovember 15

November14

4:30 In Living Color: Multispectral In Vivo ImagingRichard Levenson, M.D., Director of Research, Biomedical Systems, CRI, Inc.Small-animal imaging has a number of goals: high sensitivity, quantitative accuracy, multiplex capa-bility, depth information, high throughput, ease-of-use, physiological animal positioning, high exper-imental throughput, and so on. The Maestro™ multispectral imaging system addresses many of theseissues. One of the barriers to sensitive detection and quantitation is the presence of abundant tissueautofluorescence in the intact (skin-on) mouse. Multispectral imaging, combined with algorithmsthat can “unmix”, or separate, signals, results in targets appearing displayed against a black, near-zerobackground. Improvements in sensitivity of as much as 300-fold have been demonstrated comparedto conventional imaging systems. While moving to the NIR can reduce autofluorescence, this strat-egy limits the potential for signal multiplexing. However, a multispectral approach allows for thesimultaneous detection of at least 5 different spectrally and spatially overlapping fluorescent signals.Finally, accurate spectral unmixing allows the detection and measurement of fluorescent signals asdim 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 HuntsmanCancer Institute, University of UtahAmong the many advantages zebrafish offer is their transparency during early development andtheir small size. These features make it an attractive model for in vivo imaging. We have generateda transgenic line of zebrafish where all T cells are GFP labeled. Using multispectral imaging tech-nology we are able to follow the development, migration, and accumulation of T cells from larvalto adult stages. We have also initiated a mutagenesis screen, where we identified immunodeficientand leukemic phenotypes that are now the subject of detailed analysis and positional cloning. Inaddition, 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. Theseapproaches will be instrumental to our understanding of the molecular basis of leukemia and maycontribute to more targeted therapies for this life-threatening disease.

5:30 In Vivo Tomographic and Endoscopic Imaging ofExperimental 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 fluorescentprotease-activated near-infrared probe and multiple imaging modalities. CT-26 cells were implant-ed orthotopically into the colons of nude mice. Mice were injected with a CathepsinB-activatedprobe, imaged 24 hours later with a custom colonoscope, and with Fluorescence MolecularTomography (FMT), a novel quantitative in vivo 3D imager. Results were corroborated by excisionof the colons for ex vivo planar imaging and histology. We obtained in situ images and tumor fluo-rescence data with both endoscopy and FMT with a high tumor to background ratio and clear dif-ferentiation from the colons of control animals. Ex vivo imaging and histology confirmed the pres-ence, localization, and size of tumors. Colorectal cancer can be imaged in vivo non-invasively withprotease-activatable agents via endoscopy and 3D fluorescence tomography, validating the benefitsof these new imaging modalities in cancer research.

6:00 End of Day Two of Imaging Week

SPONSORSHIP and EXHIBIT OPPORTUNITIES

Showcase your company’s expertise, brand your solutions anddevelop revenue-generating opportunities with qualified decision-makers by exhibiting or sponsoring this event.

Sponsorship packages are designed to achieve your business devel-opment and networking goals and objectives. Sponsored opportuni-ties may include a 15-30 minute talk during the main program, break-fast or lunch. Sponsorship benefits include pre-conference, at-con-ference and post-conference marketing efforts.

For details, please contact: Carol Dinerstein, Business Development Manager

Phone: 781-972-5471 * Email: dinerstein@healthtech.com

Fluorescent Proteins in Drug Development

&In Vivo Molecular Imaging

• Save $50 off your registration.

• Your poster abstract will be published in our conference CD.

• Your research will be seen by leaders from top pharmaceutical,biotech, academic and government institutes.

Gain Further Exposure-Present a Poster

www.imaging-week.com 5

Lead Sponsoring Publications:

Web Partners:

November 15 In Vivo Molecular Imaging (continued)

11:30 A High-Throughput Molecular Imaging Screen to MonitorTherapeutic Response In Vivo

H. Charles Manning, Ph.D., Assistant Professor of Radiology, Vanderbilt University Institute ofImaging Sciences (VUIIS); Assistant Professor of Neurosurgery, Vanderbilt University Medical CenterIn this presentation we will demonstrate that molecular imaging will facilitate real-time efficacymonitoring in small animal models of experimental auto-immune encephalomyelitis (EAE) andsome forms of cancer. We have prepared a panel of complementary NIR-based imaging probes thatgive a physiologically relevant readout allowing observation of therapeutic response. These probesmeasure epidermal growth factor receptor (EGFR) expression (NIR-EGF), glucose metabolism(NIR-GLC), steroidogenesis (NIR-conPK11195), DNA replication (NIR-d-thymidine) and angio-genesis (NIR-VEGF) and apoptosis (NIR-Annexin-V). We will show that NIR-conPK11195 andNIR-GLC mimic the translational probes 18FDG and 11C-PK11195 already in use in the clinic andby utilizing our novel Lanthanide chelate chemistry, we can prepare PET/SPECT versions of theother optical probes for translation of the full efficacy screen to the clinic. It will be shown that thescreen is broadly applicable to small animal disease models and can be used to accelerate the pre-clinical evaluation of biological response modifiers (BRMs) and conventional therapeutics.

12:00 Lunch on your own(Luncheon Workshop Sponsorship Available)

1:25 Chairperson’s Remarks

Imaging in Cardiology1:30 Targeting and Tracing Antigens in Live Cells with Fluorescent

NanobodiesDr. Ulrich Rothbauer, Senior Scientist, Department Biologie II, Ludwig Maximilians UniversityFresh from the Press: Brief Communications in Nature Methods, November 2006

2:00 Functional and Molecular Imaging with Micro-UltrasoundF. Stuart Foster, Ph.D., Department of Medical Biophysics, University of Toronto, SunnybrookHealth Sciences Centre, CanadaThis presentation will describe the development, implementation, and application of high fre-quency contrast enhanced micro-ultrasound to extract quantitative measures of functional andmolecular targets in preclinical research. The development of targeted microbubble contrastagents will be described. Applications of this technology to the study of tumor microcirculationand therapeutic response to antiangiogenic agents will also be presented. Untargeted contrastpermits the evaluation the morphology and hemodynamics of various tumor models. Thesemethods allow, for the first time, realtime in vivo visualization of the true microcirculation.Molecular studies of targeted molecular targets such as VEGFR-2 will be presented. Theseresults show the ability of micro-ultrasound not only to detect expression of VEGFR-2 in exper-imental mouse tumors but also to do so with resolution nearly an order of magnitude better thanmicro PET. The feasibility of clinical translation of these approaches will also be discussed.

Imaging in Oncology2:30 Molecular Diapeutics-New Approaches to Cancer Detection

and TreatmentJamey Weichert, Ph.D., Associate Professor, Department of Radiology, Medical Physics andPharmaceutics, University of Wisconsin We have developed a radioiodinated phospholipid ether analog that has displayed striking tumoruptake and prolonged retention in 30/30 animal and human tumor models to date. We have nowsuccessfully labeled this agent with iodine-124 a new PET isotope with a 4 day half-life. A phase1 pharmacokinetic and imaging trial has been initiated in lung cancer patients and shown simi-lar tumor avidity and retention. When labeled with iodine-125, the agent, NM404, has affordedsignificant tumor regression in both human A549 lung and PC-3 prostate tumor models in micefollowing a single i.v. injection. The agent does not localize in benign or preneoplastic lesion norin inflammatory lesions and is thus only selectively retained in malignant tumor cells. Thehypothesis behind the prolonged malignant cell retention is that malignant cells lack an isoformof phospholipase-D (PLD) relative to normal host tissue cells. Because they lack this metabolic

enzyme, the agent becomes trapped in tumor cells but not in normal cells. Recently, utilizing lasercapture microdissection techniques, we have found that human pancreatic tumor cells contain275-fold less PLD than normal pancreatic host cells. This diapeutic agent is designed to exploitthis difference in malignant tumor and normal cells.

3:00 Networking Refreshment Break

3:30 Clinical and Preclinical Application of HER2-Specific AffibodyMolecules for Diagnosis of Recurrent HER2 Positive BreastCancer by SPECT or PET/CT

Dr. Anders Wennborg, Head, Pharmacology, Affibody ABThe HER2-specific Affibody molecule ZHER2:342 belongs to a novel class of small non-immunoglobulin affinity ligands with high target-binding affinity and specificity. Preclinicalcharacterization of radiolabeled HER2-Scan in mice bearing HER2-expressing tumor xenograftsshowed high specific tumor targeting with 23 % IA/g at 1 hour post injection, rapid biodistrib-ution kinetics and blood clearance and allowed high contrast gamma camera imaging as early as1 hour post injection. For the first time in human study, we evaluate the use of labeled HER2-Scan to specifically detect and stage HER2-expressing metastatic lesions in patients with recur-rent breast cancer. Injection of a microdose (<100 µg) of 111In or 68Ga-labeled HER2-Scan(110-130 MBq) resulted in high quality SPECT and PET/CT images enabling the detection ofsmall lesions(12-14 mm) after 2-3 hours post injection. Patients were carefully monitored andno adverse effects were observed.

4:00 An Early MRI Biomarker of Cancer Treatment ResponseBrian Ross, Ph.D., Professor, Department of Radiology, University of MichiganThis presentation will detail how the functional diffusion map (fDM) can be used as an imag-ing biomarker for quantification of early treatment response in solid tumors. In brief, changes intumor MRI diffusion values were found to be highly correlative with drug dose and biologicaloutcome measures revealing fDM is an effective early biomarker for prediction of efficacy inrodents and in human brain tumor patients. Thus, early fDM measurements can be used to pro-vide an early biomarker of response in patients thus allowing for an opportunity to individual-ize treatment.

4:30 Engineered Antibodies for Imaging Cell Surface PhenotypeTove Olafsen, Ph.D., Associate Researcher, Department of Pharmacology, UCLAEngineered antibodies have been developed for imaging carcinoembryonic antigen (CEA) in coloncancer, HER2 in breast cancer, CD20 in B-cell lymphoma and prostate stem cell antigen (PSCA)in prostate cancer. Recombinant antibody fragments such as diabodies (a dimer of single-chain Fv;55 kDa), minibodies (dimer of scFv-CH3; 80 kDa), and scFv-Fc (dimer of scFv-CH2-CH3; 105kDa) exhibit favorable characteristics for in vivo imaging, including rapid, specific localization toxenografts in mouse models and fast blood clearance. MicroPET imaging using fragments labeledwith Iodine-124 (t1/2 = 4.2 d) and Copper-64 (t1/2 = 12.7 h) results in high contrast images. Factorsinfluencing selection of the optimal fragment (including size, radiolabel, antigen internalization,etc.) will be discussed. Engineered antibodies recognizing cell surface targets represent a broad plat-form for developing novel imaging agents.

5:00 End of Imaging Week

Sponsoring Publications:

YES! Register me for ❒ Fluorescent Proteins in Drug Development ❒ In Vivo Molecular Imaging Keycode: 634/636 F

❒ Mr. ❒ Ms. ❒ Mrs. ❒ Dr. ❒ Prof.

NameJob Title Div./Dept.CompanyAddressCity/State/Postal Code CountryTelephone FaxEmail*Email is not a mandatory field. However, by excluding your email you will not receive notification about online access to pre-conference presenter materials, coferenceupdates and networking opportunities.

❒ I cannot attend but would like to purchase a copy of the documentation CD for $500 (plus shipping). Massachusetts delivery will include 5% sales tax.

❒ Please send information on exhibiting and opportunities to present workshops.

❒ Yes, Register me for my free trial of

PAYMENT INFORMATION

❒ Enclosed is a check or money order payable to Cambridge Healthtech Institute, drawn on a U.S. bank, in U.S. currency.

❒ Invoice me, but reserve my space with credit card information listed below. Invoices unpaid two weeks priorto conference will be billed to credit card at full registration rate. Invoices must be paid in full and checksreceived by the deadline date to retain registration discount. If you plan to register on site, please check withCHI beforehand for space availability.

❒ Please charge: ❒ AMEX (15 digits) ❒ Visa (13-16 digits) ❒ MasterCard (16 digits) ❒ Diners Club (14 digits)

Card # Exp. Date

Cardholder Signature

Cardholder’s Address (if different from above)

City/State/Postal Code Country

PRICING INFORMATION Commercial Academic, Government, Hospital-Affiliated

Full Access to Imaging Week: (November 13-15)Fluorescent Proteins in Drug Development and In Vivo Molecular Imaging

Early Registration Discount until September 1, 2006 ❒ $1445 ❒ $775Advance Registration Discount until October 6, 2006 ❒ $1595 ❒ $850Registrations after October 6, 2006 and on-site ❒ $1795 ❒ $925Poster Discount ❒ $50 off ❒ $50 off

2 Day ConferenceEarly Registration Discount until September 1, 2006 ❒ $1045 ❒ $545Advance Registration Discount until October 6, 2006 ❒ $1195 ❒ $620Registrations after October 6, 2006 and On-site ❒ $1395 ❒ $695

*Required Please select the conference you’re attending:❒ Fluorescent Proteins in Drug Development ❒ In Vivo Molecular Imaging Poster Discount ❒ $50 off ❒ $50 off

REGISTER 3 — 4th IS FREE Individuals must register for the same conference orconference combination and submit completed registration forms together for dis-count to apply. Please reproduce this registration form as needed.

FAX OR MAIL YOUR REGISTRATION TO:Cambridge Healthtech Institute250 First Avenue, Suite 300, Needham, Massachusetts 02494 T: 781-972-5400 or toll-free in the U.S. 888-999-6288 F: 781-972-5425 • www.healthtech.com

Please send information about these CHI conferences:

❒ Targeted Nanodelivery (NNO)

❒ High Content Analysis Europe (HCAE)

❒ High-Content Analysis (HCA)

PRESENT A POSTER AND SAVE $50

Cambridge Healthtech Institute encourages attendees togain further exposure by presenting their work in the postersessions. To secure a poster board and inclusion in the conferenceCD, your abstract must be submitted, accepted and regis-tration paid in full by October 24, 2006. Register online touse the Poster Abstract Submission form or, if you register byphone, fax, or mail, you will receive Poster AbstractSubmission guidelines via email.

I am interested in presenting a poster at ❒ Fluorescent Proteins in Drug Development❒ In Vivo Molecular Imagingand will submit a completed one-page abstract byOctober 24, 2006. (Please Note: Registration must be paidin full to present poster.)

Title

CHA ADVANCES REPORTSAffiliate authors collaborate with CHA experts to provide a series of reports that evaluate the salient trends in phar-maceutical technology, business, and therapy markets. For moreinformation, visit www.advancesreports.com, or contact RobertEnglish, renglish@chacorporate.com, 781-547-0188.

ADDITIONAL REGISTRATION DETAILSEach registration includes all conference sessions, posters andexhibits, food functions, and a copy of the conference CD.

GROUP DISCOUNTSSpecial rates are available for multiple attendees from the sameorganization. Contact David Cunningham at 781-972-5472 to discuss your options and take advantage of thesavings.

HANDICAPPED EQUAL ACCESSIn accordance with the ADA, Cambridge Healthtech Instituteis pleased to arrange special accommodations for attendees withspecial needs. All requests for such assistance must be submit-ted in writing to CHI at least 30 days prior to the start of themeeting.

SUBSTITUTION/CANCELLATION POLICYIn the event that you need to cancel a registration, you may:• Transfer your registration to a colleague within your organi-

zation• Credit your registration to another Cambridge Healthtech

Institute program• Request a refund minus a $100 processing fee per

conference• Request a refund minus the cost ($500) of ordering a copy

of the CDNOTE: Cancellations will only be accepted up to two weeksprior to the conference.

Program and speakers are subject to change

Video and or audio recording of any kind is prohibited onsite at all CHI events.

Third Annual

Fluorescent Proteinsin Drug DevelopmentNovember 13-14, 2006Hilton La Jolla Torrey Pines • La Jolla, CA

Third Annual

In Vivo Molecular ImagingMoving from Discovery to Preclinical to Clinical Applications

November 14-15, 2006Hilton La Jolla Torrey Pines • La Jolla, CA

TO REGISTER: WEB: www.imaging-week.com • PHONE: 781-972-5400 or toll-free in the U.S. 888-999-6288 • FAX: 781-972-5425 • MAIL: 250 First Avenue, Suite 300, Needham, MA 02494

Please refer to the Keycode below:

Best

Va

lue

Yes! I would like a free subscription to: