Imaging remains an important tool in oncology drug discovery and development. This noninvasive technology delivers significant time and cost reduction when used systematically and skillfully. Cambridge Healthtech Institute’s Imaging in Cancer Drug Development is designed to bring together leading imaging experts from industry and academia, as well as scientists and clinicians who use their services to accelerate cancer research.

Final Agenda

Wednesday, June 10

7:00 am Registration and Morning Coffee

TRANSLATIONAL IMAGING IN ONCOLOGY

7:55 Chairperson’s Opening Remarks

Paul McCracken, Ph.D., Director of Imaging, Biomarkers and Personalized Medicine CFU, Eisai

8:30 Session Break

8:35 Improving Decision Making For Drug Discovery and Early Development In Oncology With Imaging

Paul McCracken, Ph.D., Director of Imaging, Biomarkers and Personalized Medicine CFU, Eisai

Due to high cost and low probability of success, the pharmaceutical industry needs to improve the decision making process for compounds entering Phase I, better using Phase I studies for decision making beyond safety, and improving the quality of compounds entering clinical trials. Imaging biomarkers can significantly contribute to the decision making process, such as supporting target engagement, proof of concept, drug safety, patient selection, and dose selection.

9:05 Enabling Translational Cancer Research and Drug Development Through The Integration Of Preclinical Imaging

Quang-Dé Nguyen, Ph.D., Director of the Lurie Family Imaging Center, Senior Scientist, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute

The Lurie Family Imaging Center (LFIC), the preclinical arm of the Center for Biomedical Imaging in Oncology (CBIO) at the Dana-Farber Cancer Institute, is a state-of-the-art imaging facility that conducts interdisciplinary in vivo translational and experimental therapeutics studies focused on cancer, with an emphasis on assessment of novel cancer therapeutics, multimodality imaging of cancer, molecular imaging of pharmacodynamic efficacy, development of novel probes and target validation.

9:35 Click-mediated Therapy for HER2-positive Breast Cancer

Dmitri Artemov, Ph.D., Associate Professor, Radiology and Oncology, The Johns Hopkins University School of Medicine

Treatment of HER2-positive tumors that have innate or acquired resistant to trastuzumab is an important clinical problem. Here we report a two-component delivery system for induced internalization of HER2-targeted nanocarriers with therapeutic cargo based on click-chemistry in situ reaction between the pretargeting and therapy carreir components. This pretargeting strategy provides image guidance for therapeuetic applications and has been validated in preclinical models of breast cancer.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

ANALYSING AND LEVERAGING RESULTS

10:45 Chairperson's Remarks

Neal Goodwin, Ph.D., Director, Corporate Research Development, Champions Oncology

10:50 Statistical Analysis of PDX Studies and Preclinical Phase-II-Like Trials (PP2T) at EMD Serono

Anderson Clark, Ph.D., Director, In vivo Pharmacology, Oncology, EMD Serono Research & Development Institute

At EMD Serono, we use PDX models in Preclinical Phase 2-Like Trials (PP2T) to support Phase 2 clinical decisions for which the use of statistics has become paramount. Working closely with clinical biostatisticians, we have developed statistical approaches to different aspects of the trials which will be discussed, such as trial design, relationships between preclinical responses and RECIST criteria, responses and how to measure them, and determining treatment differences.

11:20 The Art of the Cocktail: Optimizing Multidrug Combinations in Preclinical Studies

Arijit Chakravarty, Ph.D., Director, Modeling & Simulation (DMPK), Takeda Pharmaceutical International Co.

The design of optimal combinations relies on maximizing combination efficacy for a given toxicity budget. This presentation will describe the development of novel mathematical modeling methods (based on tricks used by bartenders to develop recreational cocktails), to visualize and design efficient studies for two-drug (and higher-order) combinations, and their application in a practical drug development context, showing their impact on actual study design, and validation with in vivo datasets.

11:50 Evaluating Efficacy Coupled with Toxicity in a Preclinical Model of Head and Neck Cancer

Benjamin G. Cuiffo, Ph.D., Scientist, Biomodels, LLC

Chemoradiation used for the treatment of HNC results in regimen- related mucosal toxicity (mucositis) which impedes optimum cancer therapy and causes significant physiologic and resource adversities. We present a new, highly translational animal model which simultaneously assesses both the targeted efficacy of new anti-tumor agents and their impact on mucositis.

12:05 pm Can Animal Study Software Technology That Emulates Clinical Trial Methods Improve the Predictability of Clinical Outcome?

Eric Ibsen, Vice President, Studylog Systems, Inc.

The 95% failure rate of anticancer therapeutic approvals after positive Phase III trials suggests that existing pre-clinical approaches and tools are suboptimal predictors of clinical outcome. Recent software innovations enable animal researchers to mirror multi-arm, multi-site, clinical trials with rolling enrollment and run “piggy-backed” studies under a common protocol.

12:20 LUNCHEON PRESENTATION: 2nd Generation PDX Models Can Help the Progression of Precision Medicine

Jean-François Mirjolet, Ph.D., Technology Director, Oncodesign

Panels of PDX models reflecting the genetic diversity of human cancers can increase the predictivity of patients’ tumor response to treatments. But there is still a critical need for better predictive models for novel agents targeting the tumor microenvironment. In addition to the well characterized syngeneic models used for immuno-oncology drug testing, Oncodesign developed highly refined PDX models in microenvironment-humanized mice, demonstrating usefulness in PDX tumor dissemination and immuno-oncology research.

1:00 Refreshment Break in the Exhibit Hall with Poster Viewing

IMAGING ADVANCES AND END POINTS IN CANCER RESEARCH

1:30 Chairperson’s Remarks

Susanta Sarkar, Ph.D., Adjunct Associate Professor, Radiology, University of Pennsylvania; President, CadenzaMed LLC

1:35 Translational Imaging in Oncology

Daniel P. Bradley, Ph.D., Head of Biomedical Imaging at Takeda Boston, Takeda Pharmaceuticals International Co.

Daniel will present on a number of programs that he has directly worked on, or working on, that have been developed in translational imaging in oncology. Importantly, this talk will highlight important lessons learned about collaboration, timing, perspectives and science with a hope that other groups in the imaging community can leverage this information for future developments. The Biomedical Imaging Group balances its portfolio between the use of conventional imaging biomarkers used in a novel biological and/or pharmacological context to advanced imaging techniques.

2:05 Non-Invasive and Simultaneous Measurement of Pharmacokinetics and Pharmacodynamics in Preclinical Cancer Models

Werner Scheuer, Research Leader, Pharma Research and Early Development, Discovery Oncology, Roche Diagnostics GmbH

Non-invasive imaging modalities (optical and micro-computed tomography) in combination with ex vivo analysis (3D-multispectral fluorescence microscopy, FACS) are an undispensable tool to assess the anti-tumoral efficacy of new compounds. Proliferation of tumor cells, metastasis, angiogenesis, and induction of apoptosis as well as phosphorylation of kinases can be monitored in mice carrying tumor cells s.c. or orthotopically. The quantification of these pharmacodynamics (Pd) read-outs are combined with optical pharmacokinetics (Pk). The simultaneous measurement of Pd and Pk reduces the number of animals significantly and provides a comprehensive evaluation of new drugs.

2:35 Normalizing Tumor Microvasculature and Microenvironment

Dai Fukumura, M.D., Ph.D., Deputy Director, Edwin L. Steele Laboratory; Biologist, Department of Radiation Oncology, Massachusetts General Hospital; Associate Professor, Harvard Medical School

Intravital microscopy techniques and sophisticated animal models have been providing unprecedented molecular, cellular, anatomical and functional insights in tumor biology. Tumor microvasculature is structurally and functionally abnormal hindering drug delivery and inducing a hostile microenvironment that causes ineffectiveness of anti-tumor treatments. Imbalance of pro- and anti-angiogenic factors is causing these pathophysiological features in the tumor. Hence, restoring the balance of these factors in tumors may “normalize” tumor vasculature, improve its function and microenvironment, and enhance the efficacy of cytotoxic therapies.

3:05 Companion Diagnostic Co-Development Models

Susanta Sarkar, Ph.D., Adjunct Associate Professor, Radiology, University of Pennsylvania; President, CadenzaMed LLC

A number of antibody-drug conjugates (ADC) are currently in clinical trials driven by recent technological progress. However, most ADC targets are not universally expressed on a given tumor type and will require a companion diagnostic to select patients that are likely to benefit from the particular ADC. A non-invasive imaging-based companion diagnostic will allow real time measurement of antigen expression in the tumor, thus enabling patient stratification in real time by identifying patients who are likely to respond to the ADC.

3:35 Light In and Sound Out: High Resolution Deep Tissue Imaging Via Multispectral Optoacoustic Tomography Imaging

Neal C. Burton, Ph.D., Senior Application Specialist, iThera Medical

Multispectral optoacoustic tomography (MSOT) imaging opens up a wide field of research for development of novel tumor markers and therapeutic agents, dynamic contrast enhancement, and toxicological assessment of novel pharmaceuticals in small animal models. Initial results of MSOT clinical imaging studies are also showing high potential for clinical translation.

4:05 Refreshment Break in the Exhibit Hall with Poster Viewing

Thursday, June 11

CASE STUDIES

8:30 Chairperson’s Remarks

Jonathan Wall, Ph.D., Professor of Medicine, Human Immunology and Cancer Program; Director, Amyloid and Preclinical Molecular Imaging Laboratory, University of Tennessee Graduate School of Medicine

8:35 Preclinical Development of Peptide Radiotracers for Detecting Visceral Amyloid Associated with Multiple Myeloma

Jonathan Wall, Ph.D., Professor of Medicine, Human Immunology and Cancer Program; Director, Amyloid and Preclinical Molecular Imaging Laboratory, University of Tennessee Graduate School of Medicine

Multiple myeloma, the second most common hematologic malignancy in the US, and related plasma cell dyscrasias, are characterized by the secretion of monoclonal immunoglobulin light chains that often deposit as insoluble amyloid fibrils in visceral organs. The abundance of amyloid deposits and their anatomic distribution often inform prognosis and treatment options. At present there are no clinical methods for the non-invasive, quantitative measurement of amyloid. To this end we have generated synthetic, poly-basic peptides that preferentially bind amyloid and, when radiolabeled, can be used for disease detection by molecular imaging.

9:05 PARP1 Status Annotation in Cancers of the Oral Cavity

Thomas Reiner, Ph.D., Assistant Member, Memorial Sloan-Kettering Cancer Center; Assistant Attending Chemist, Radiochemistry & Imaging Sciences Service; Assistant Professor, Weill Cornell Medical College

The enzyme PARP1 has attracted attention for its diagnostic and prognostic value, and quantification of PARP1 expression could impact the clinical decision-making process directly. A noninvasive imaging tool that can unambiguously quantify the expression of PARP1 in vivo, however, is an unmet clinical goal. Here, we report on the use of a PARP1 imaging agent as a probe for the early detection of oral cancer, discuss its pharmacological properties and selectivity in vivo, and illustrate its potential impact on future clinical research.

9:45 Utility of 3D Ultrasound and Photoacoustic Imaging in Subject Stratification and Treatment Prediction

Srivalleesha Mallidi, Ph.D., Research Fellow, Laboratory of Tayyaba Hasan, Harvard-MIT

Prediction of response and tumor recurrence following a given therapy is necessary for effective treatment. In this talk, we demonstrate an approach towards this goal with an example of photodynamic therapy (PDT) as the treatment modality and photoacoustic imaging (PAI) as a non-invasive, response and disease recurrence monitor in a murine model of glioblastoma (GBM). PDT is a photochemistry-based, clinically used technique that consumes oxygen to generate cytotoxic species thus causing changes in blood oxygen saturation (StO2).

10:15 Proteomic Imaging of Caveolae to Penetrate Solid Tumors

Jan E. Schnitzer, M.D., Director, Professor of Cellular & Molecular Biology, PRISM, Proteogenomics Research Institute for Systems Medicine

Access inside solid tumors is poor yet critical for imaging and therapeutic agents to be effective. These agents rely on passive movement across endothelial barriers to reach targets inside tumors. Our “proteomic-imaging” efforts discovered a new pathway and class of delivery targets for active transport into tumors. In vivo imaging reveals caveolae-targeted antibodies, drugs, imaging agents, and nanoparticles being pumped across endothelium to achieve >100-fold more tumor delivery and efficacy.

10:45 Coffee Break in the Exhibit Hall with Poster Viewing

Image guided interventions

11:30 Mass Spectrometry for Image-Guided Therapy

 Nathalie Y.R. Agar, Ph.D., Assistant Professor of Neurosurgery, Assistant Professor of Radiology, Harvard Medical School, Director, Surgical Molecular Imaging Laboratory, Department of Neurosurgery, Brigham and Women's Hospital 

12:30 Close of Conference