Biomedical Imaging

Summary

Molecular imaging has become an increasingly indispensable tool in life sciences basic research, in translational medicine, and in routine medical diagnostics. This Biomedical Imaging report covers its top applications areas: medical diagnosis and translational research both relevant to pharmacology and drug development. This report:

• Reviews the current and emerging technologies of bioimaging
• Focuses on the use of molecular imaging in drug discovery and development from cell-based screening to clinical trials
• Presents clinical and diagnostic applications in use today and tomorrow's trends
• Evaluates regulatory issues surrounding validating molecular imaging biomarkers
• Provides profiles of industry players that develop and/or market equipment or probes for cellular, small animal, or clinical imaging
• Provides projections of likely bioimaging developments that will drive the field during the 2010s

Today, bioimaging technologies are not only a valuable tool for translational research; they have become an integral part of defining how, and with which precise goal in mind, drugs and medical devices are developed. Imaging has reached far upstream into the drug development pipeline, pervading preclinical and discovery-stage animal studies and reaching back to the earliest stages: lead optimization and even compound screening. In clinical studies, bioimaging has become all but omnipresent, providing an enormous amount of patient-specific information that, if linked to clinical and behavioral parameters, can often aid in a proof-of-concept understanding of investigational drugs.

Figure

Biomedical Imaging: From Drug Target Discovery to Medical Diagnostics describes the technologies of bioimaging, which have evolved to visualize a broad variety of functional parameters, mapping them to anatomical structures that are thereby ""tagged"" with additional information of high biological relevance. Equipment and methodology are diverse, comprising the most advanced confocal microscopes for spotting intracellular fluorescence signals, ultrasound probes with computerized attenuation correction, scanners that combine PET or SPECT with x-ray CT or MR, near-infrared optical molecular imaging, and ""4D"" time series of 3D reconstructions from tomographic slices.

This report addresses the use of molecular imaging in drug discovery and development from cell-based screening to clinical efficacy trials, now and into the next decade. Applications to the pharmaceutical industry start with target and lead discovery and characterization, continue into translational research, and end with therapy monitoring for approved drugs.

Biomedical Imaging: From Drug Target Discovery to Medical Diagnostics analyzes diagnostic bioimaging uses in the physician's office or nuclear medicine centers, including cancer staging, planning, and response assessment; cardiorespiratory and vascular imaging; neuroimaging; and molecular imaging for eye diseases, arthritis, diabetes, and HIV. The report also discusses the market parameters for PET procedures, which are the key economic driver for clinical molecular bioimaging.

The US FDA has developed detailed rules for every aspect of diagnostic bioimaging and specific rules for PET tracers and tomographic scanners. This report reviews the regulatory background and analyzes the problems faced in validating imaging molecular biomarkers and getting them accepted. Also included are results from a Web survey that outlines the expectations of researchers and managers in the molecular bioimaging field.

Biomedical Imaging: From Drug Target Discovery to Medical Diagnostics concludes with projects of likely developments that will drive this fascinating field during the 2010s.

Contents

• Chapter 1
• Rendering Living Objects by Invisible Properties: The Technologies of Bioimaging
  • 1.1. Mapping Signals from Molecular Responses and Interactions
  • Three Dimensions Compressed into Two
  • Tomography: Virtual Slicing and Reconstruction
  • Three-Dimensional Reconstruction and Rendering of Tomographic Images
  • 1.2. Computed X-Ray Tomography
  • 1.3. Magnetic Resonance Imaging
  • 1.4. Isotope Imaging: Pet and Spect
  • Single-Photon Emission Computed Tomography
  • Positron Emission Tomography
  • 1.5. Optical Techniques: Fluorescence, Bioluminescence, and Optical Pet
  • Fluorescence and Bioluminescence-Base Imaging
  • Diffuse Optical Imaging
  • Optical Coherence Tomography
  • Confocal Laser Scanning Microscopy and Its Derivatives
  • Spectroscopic Imaging Technologies
  • Optical Spectroscopy
  • Imaging Based on Multichannel near-Infrared Spectroscopy
  • Frap and Flip
  • 1.6. Other Imaging Technologies and Overarching Approaches
  • Ultrasound and Photoacoustics
  • Imaging and Nanotechnology
  • Brain Mapping with Endogenous Fields and Electrodes
• Chapter 2
• Molecular Imaging in Translational Research
  • 2.1. Optical Molecular Imaging Tags: from Discovery to Design
  • Fluorescent Proteins
  • Bioluminescence
  • Target-Activated Probes and Proximity Assays
  • Quantum Dots
  • 2.2. Cellular-Level Molecular Imaging in Drug Discovery and Target Characterization
  • Cell-Based High-Content Screening Versus Cellular Molecular Imaging
  • 2.3. Small Animal Imaging
  • The Sair Program in The United States, and Other Significant Small Animal Imaging Sites
  • Classical Microtomographic Technologies
  • Optical Imaging of Laboratory Animals
  • Ultrasound Imaging of Research Animals
  • 2.4. Molecular Imaging Applications in Predictive Safety Technologies
  • 2.5. Imaging in Clinical Trials: Present and near Future
  • A Catalog for Potential Clinical Imaging Biomarkers
  • Science and Logistics: Formidable Challenges for Sponsors and Sites
  • Alzheimer's Disease
  • Multiple Sclerosis
  • Molecular Imaging in Cancer Trials: A Large Field Still to Be Explored
  • Stem Cell and Gene Therapies
  • Atherosclerosis
• Chapter 3
• Diagnostic Imaging at Nuclear Medicine Centers and at The Doctor's Office
  • 3.1. Key Market Characteristics for Clinical Nuclear Medicine Imaging
  • 3.2. Cancer Staging, Therapy Planning, and Response Assessment
  • Solid Tumors: The Largest Field for Imaging
  • Lung Cancer
  • Optical Breast Imaging: beyond Digital Mammography
  • Urological Cancers: Prostate and Bladder Tumors
  • Melanoma
  • Limited Potential for Molecular Imaging in Difficult-to-Treat Cancers
  • New Developments in Colonoscopy
  • 3.3. Cardiorespiratory and Vascular Imaging
  • Inflammatory Lung Diseases
  • Imaging Agents for Cardiac Stress Testing and Heart Failure
  • Nuclear Imaging of Atherosclerotic Plaque
  • 3.4. Neuroimaging
  • Dementia
  • Parkinson's Disease and Attention Deficit Disorder
  • Multiple Sclerosis
  • Pain and Inflammation
  • 3.5. Imaging in Eye Diseases
  • 3.6. Arthritis, Osteoarthritis, and Gout: from Structure to Function
  • 3.7. Diabetes: A Challenging Crossover Case for Molecular Imaging
  • 3.8. Hiv Tropism: A Clniical Application of Cellular Molecular Imaging
• Chapter 4
• Molecular Imaging and Regulatory Authorities
  • 4.1. Fda Regulations of Medical Imaging Agents
  • 4.2. Specific Fda Regulations of Pet Tracers
  • 4.3. Molecular Imaging Feels The Crunch from The Deficit Reduction Act Reimbursement Cut
  • 4.4. Regulation of Tomographic Scanners and Picture Archiving Systems
  • Tomographic Scanners
  • Picture Archiving Systems
  • 4.5. Molecular Imaging Data as Endpoints in Drug Trials
  • Reading of Imaging Data in Clinical Trials
  • Training of Readers
  • Blinding of Readers
  • Submission and Regulatory Review of Imaging Data
  • 4.6. European Regulatory Positions on Molecular Imaging
• Chapter 5
• Selected Players in The Molecular Imaging Business
  • 5.1. Cellular Imaging Equipment and Software Vendors
  • Carl Zeiss
  • Apotome Imaging System
  • Cell Observer Hs
  • Laser Scanning Microscopes
  • Leitz
  • Total Internal Fluorescence Microscopy System
  • Super-Resolution Confocal/Multiphoton Systems
  • Olympus
  • Nikon
  • Perkinelmer
  • Caliper Life Sciences
  • Visen Medical
  • Mauna Kea/Cellvizio
  • Visualsonics
  • Media Cybernetics
  • 5.2. Manufacturing of Preclinical and Clinical Molecular Imaging Equipment
  • Ge Healthcare
  • Siemens Healthcare
  • Philips Healthcare
  • Bruker
  • Biospace Lab
  • Berthold Technologies
  • Positron
  • Digirad
  • Carestream Health
  • Li-Cor Biosciences
  • 5.3. Developers of Imaging Agents and Probes
  • Bayer Schering Pharma
  • Siemens Medical Solutions
  • Ge Healthcare
  • Lantheus Medical Imaging
  • Alseres Pharmaceuticals
  • Aposense
  • Avid Radiopharmaceuticals
  • Kereos
  • Molecular Insight Pharmaceuticals
  • Fluoropharma
  • Invitrogen
  • Advanced Research Technologies
  • Aion Diagnostics
• Chapter 6
  • Cellular Molecular Imaging, Clinical Biomarkers, and Image Analysis: A Perspective for The 2010s
  • 6.1. Role of Cellular Imaging in Drug Discovery and Development
  • 6.2. Imaging Biomarkers
  • 6.3. Information Technology and Imaging: The Overarching Tool
  • Appendix A
• Molecular Imaging Resources
  • Societies, Transnational Institutions, and Conferences
  • Journals and Databases
  • Industry Magazines
  • Databases
  • Appendix B
  • Insight Pharma Reports Molecular Imaging Survey-november 2008
  • References
  • Company Index with Web Addresses
  • Tables
  • Table 2.1. Vendors of Small Animal Ct, Mri, Pet, and Spect Equipment and Their Microtomographic Products
  • Table 2.2. Vendors of Small Animal Ct, Mri, Pet, and Spect Equipment and Their Products for Optical Imaging
  • Table 3.1. US Market Data and Projections for Pet Procedures and Equipment
• Figures
  • Figure 1.1. Principle of Tomographic Imaging
  • Figure 1.2. Principle of Magnetic Resonance Imaging
  • Figure 1.3. Principle of Positron Emission Detectable by Tomography
  • Figure 1.4. Schematic Representation of The Confocal Microscopy Principle
  • Figure 1.5. Schematic Representation of The IMS Principle
  • Figure 2.1. Fluorescence Resonance Energy Transfer (Fret) Principle
  • Figure 2.2. Flex Triumph: An Example of A Ct/Pet/Spect Multimodal Small Animal Scanner
• Appendix Figures
  • Figure 1a. Definition of Molecular Imaging
  • Figure 2a. Response by Sector
  • Figure 3a. Response by Title
  • Figure 4a. Experience with Molecular Imaging
  • Figure 5a. Number of Molecular Imaging Procedures Conducted
  • Figure 6a. Molecular Imaging Studies for Drug/Imaging Agent Development
  • Figure 7a. Stage of Drug Development at Which Molecular Imaging Studies Are Conducted
  • Figure 8a. Molecular Imaging Data Integration into Regulatory Submissions
  • Figure 9a. Biological Systems Targeted
  • Figure 10a. Molecular Imaging Techniques Used
  • Figure 11a. Purposes for Use of Molecular Imaging Techniques
  • Figure 12a. Potential for Molecular Imaging
  • Figure 13a. Rate-Limiting Technical Factor of Molecular Imaging
  • Figure 14a. Rate-Limiting External Factor in The Commercialization of Molecular Imaging