Abstract
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.
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.
Table of 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
