Bioimaging Focus Area 2007

BioLogue Focus Areas 2007 Bioimaging

What is bioimaging? ..........................................................................................................................2 Molecular Bioimaging.....................................................................................................................2 Biomedical imaging .......................................................................................................................2 Computational Bioimaging .............................................................................................................2 Bioimaging in Drug Discovery.........................................................................................................3 Why is bioimaging important to Biomedical R&D? ................................................................................3 What is the goal of the Bioimaging Focus Area?...................................................................................4 How does this goal match existing funding opportunities? ....................................................................4 Conclusion........................................................................................................................................5

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What is bioimaging?

Bioimaging Focus Area 2007

Bioimaging is a broad field with many different aspects or areas, and we wish to explore many of them in our overview event on June 7, 2007, by focusing on regional (university, hospital and industry-based) expertise. Consulting local experts, we have identified four main areas, listed below. While there is overlap among these areas, we also recognise that innovation is found most often at these areas of overlap between disciplines. These four major areas cover the basic research, hospital application, computational analyses and Pharma aspects of bioimaging. The areas identified are: Molecular Bioimaging Molecular imaging technologies are being developed to examine the integrative functions of molecules, cells, organ systems and whole organisms. The organisms range from viruses to bacteria to higher order species, including humans, and in each case, molecular imaging is used to examine the structure and regulatory mechanisms of their organised functions. Molecular imaging technologies use molecular probes or interactions with molecules. Many different technologies have been and continue to be developed to image the structure and function of systems, such as optical/fluorescence imaging, positron emission tomography (PET), magnetic resonance imaging (MRI), X-ray computed tomography (CT), single photon emission computed tomography (SPECT), ultrasound and microwave. All have unique applications, with advantages and limitations. Biomedical imaging Biomedical imaging refers to methods that open new ways to see the bodys inner workings, measure biological functions, and evaluate cellular and molecular events using less invasive procedures. While X-ray imaging is a familiar example, it represents only one aspect of this fast growing field. Examples of other imaging modalities include: Magnetic resonance imaging (MRI) Positron emission tomography (PET) Single photon emission coherence tomography (SPECT) Ultrasound imaging Optical coherence tomography (OCT) Computed (x-ray) tomography Fluorescence imaging

These approaches allow physicians to detect disease and injury at their most curable stage and enable the delivery of less invasive and highly targeted medical therapies. Cellular and molecular imaging techniques combine new molecular agents with traditional imaging tools to capture pictures of specific biological pathways and processes in a living organism. These approaches help researchers study normal biological processes and to diagnose and manage diseases. Computational Bioimaging Advanced, multimodal imaging techniques, powered by new computational methods, are changing the face of biology and medicine. These new imaging modalities produce information about anatomical structure that is linked to functional data, as described by electric and magnetic fields, mechanical motion, and metabolism. This integrated approach provides comprehensive views of the human body in progressively greater depth and detail, while gradually becoming cheaper, faster, and less invasive. As a result, imaging

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becomes more common, more familiar, which in turn produces new scientific specialties that rely on particular combinations of imaging, computer science, and medicine.

Bioimaging Focus Area 2007

As these imaging methods develop, the extent of their effectiveness and impact relies on a new kind of scientist. This new scientist combines expertise in anatomy and physiology with a specific set of skills in physics, mathematics, bioengineering, and computer science. The result is a person who is qualified to study computational bioimaging. Another distinctive feature of this new interdisciplinary scientist is the ability to effectively collaborate among experts in bioengineering, computation, and the biosciences - a relationship that accelerates and benefits biomedical research and development. Bioimaging in Drug Discovery Bioimaging enables the discovery and tracing of biomarkers of drug response - an increasingly important field of research in the pharmaceutical industry. The Food and Drug Administration (FDA), the National Cancer Institute (NCI), and the Centers for Medicare and Medicaid Services (CMS) have agreed to collaborate on improving the development of cancer therapies and outcomes for cancer patients through biomarker development and evaluation (See http://www.fda.gov/oc/mous/domestic/FDA-NCI-CMS.html). A similar effort across the National Institutes of Health's (NIH's) Institutes and Centers (ICs) is being planned. Biomarkers are biological indicators of disease or therapeutic effects that can be measured by in vivo biomedical imaging and molecular imaging in particular, as well as other in vitro or laboratory methods. Recent work has shown that biomedical imaging can provide an early indication of drug response by use of X-ray, CT or PET-CT. Many sources of uncertainty exist in imaging as a biomarker. Biological variability, for example, is a factor both drug- and patient-dependent and thus difficult to characterize or model. However, other uncertainties are associated with the image data collection platform and the robustness of software tools required for reliable, quantitative measurement of change over time, such as tumour volume, radioactive tracer activity, or contrast agent dynamics. All these sources of uncertainty significantly affect the statistical power of clinical drug or therapy trials. The development of standards for image quality control, image data collection, and benchmarking of change analysis software tools, as well as image-specific statistical methods, could significantly reduce the size of clinical trials for drug response. The costs of a drug submission to the FDA by the pharmaceutical industry may soon exceed $1 billion. The use of standardized imaging methods may reduce these trial costs.

Why is bioimaging important to Biomedical R&D?

Living systems have the ability to respond to changing environmental and physiological conditions in a dynamic fashion. Imbalance of these processes leads to disturbed development and disease. The complex cellular and molecular signalling and regulatory processes underlying development and homeostasis can only be understood comprehensively by analysis in the intact living organism. Molecular interactions are frequently transient and context-dependent, necessitating in vivo analysis to generate relevant insights into the molecular mechanisms. Biomedical research and drug development have thus an increasing need to analyse and monitor these dynamic processes in cellular physiology, development and disease in the living organism using bioimaging technologies. For example, MRI and PET are technologies that allow precise tracking of metabolites which can, in turn, be used as biomarkers for disease identification, progress, and treatment response. Discovery and development of disease biomarkers in animal models can then be transferred to use in clinical settings. Finding the correct imaging technologies those with the resolving power, the sensitivity, and the transferability from animals to man is the first phase in the creation of biomedical imaging R&D units to serve the drug discovery industry and, ultimately, the patients who can benefit.

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What is the goal of the Bioimaging Focus Area?

Bioimaging Focus Area 2007

The goal of Bioimaging Focus Area is to expand everyones R&D networks, to achieve a critical mass of connections for R&D innovation in bioimaging to explode. BioLogue intends to bring together biomedical research companies and university & hospital teams from the Greater Copenhagen Area (GCA) that are interested in collaborating on bioimaging research, development and use. A GCA Bioimaging consortium would provide a platform of instruments, technologies and know-how that is not present in individual institutes or companies, and would generate a scientific environment of international standards and competitiveness. The consortium would combine the expertise to not only use bioimaging techniques but also to modify both the hardware and the software according to the needs of the research and users. For example, in pre-clinical research we need to: Develop standards for imaging technologies Establish and strengthen units that use imaging technologies in animal models (MRI, microPET, etc) Develop tools for processing and analysis of data from imaging technologies

In disease-specific research there are many possibilities for public-private collaboration, such as: Research for the early detection and treatment of rheumatoid arthritis via biomarkers and bioimaging. Research and use of imaging technologies in cancer detection, for creation of blood vessels (angiogenesis), and cancer monitoring, for spreading of tumours and programmed cell death (apoptosis) Imaging of structure and function in the brain to identify responding patients in clinical trials for treatment of dementia, stroke, Parkinsons disease, multiple sclerosis and psychiatric conditions. Use of imaging technologies to identify areas affected by pain, for the monitoring of the efficacy of new treatments and new drug over time. Use of beta-cell specific ligands in diabetes research.

In the realm of nanotechnology, drug delivery to specific targets, controlled drug release and monitoring offers opportunities for molecular imaging technologies to make significant impacts on both pharmacology and early clinical trials.

How does this goal match existing funding opportunities?

Next to recruitment of patients to clinical trials, identification and validation of biomarkers is the second highest priority of the European research agenda to re-gain a competitive advantage in pharmaceutical R&D. (See both Innovative Medicines Initiative and its Strategic Research Agenda) Note also that identification and validation of biomarkers relies so heavily on new techniques in bioimaging, that the IMI SRA calls for disease-specific European centres of imaging technologies. At these centres, new imaging technologies and their applications can be proven through validation collaborations involving hospitals and their patients, regulatory authorities, industry, and academia. One possible model for funding these initiatives is shown in Figure 1.

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Bioimaging Focus Area 2007

Figure 1: Potential financing model for forthcoming European research projects (Innovative Medicines Initiative: Strategic research Agenda).
As one of the keys to gain a competitive advantage in biomedical/medico R&D via biomarkers, bioimaging is an essential area for public-private collaboration. Its importance is also reflected in the other European funding opportunities (FP7/JTP). Significant areas for European research are stipulated as: Diagnostic & prognostic markers for inflammation & tissue damage Surrogate markers for drug efficacy and safety Markers of host-defence and risk-benefit evaluation etc. Markers for functional recovery or disease modification Predictive genotyping Population screening not only through genetics but also other technologies that can provide a high degree of specificity and sensitivity Pharmacogenetic markers of inflammatory disease groups to subtype responders/non-responders (improved efficacy/safety ratio/predictive adverse effect risk) Pharmacogenetics (patients, ex: allotype responses to antibodies) 5 years Polyomics Pharmacogenomics (diseases) 20 years Imaging: Monitor Disease progression (MRI)

Significant areas for validation and standardisation are: Establishment of European standards for validation of markers Coordination of national networks, tissue banks, clinical expertise, SMEs discovery and Pharma Regulatory standards and dialogue/ acceptance of validation

Conclusion
Bioimaging technologies offer unique funding opportunities for public-private partnering in biomedical R&D. BioLogues Bioimaging Focus Area and its initiatives, such as the Bioimaging Science Dating Event, aims to gather interested academic, hospital, regulatory and industry participants from across the region to discover not only one another but also to take the lead in bioimaging innovation. If you have questions, please contact David Featherston at +45 28 75 65 74 or david@biologue.org

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