Advances in Imaging Biomarkers:
Innovative technologies, applications in R&D and clinical practice, and informatics and regulatory requirements
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| Overview: | |
| Imaging biomarkers, those quantified using imaging modalities including Magnetic Resonance Imaging and Positron Emission Tomography, are attractive for a variety of reasons: the methods of measurement used are non-invasive, and can provide information that cannot be obtained in other ways including a drug’s pharmacology and side effect profile, interaction of a drug and its target, delivery of a drug to its target, and the drug’s pharmacokinetic profile. In the clinical setting, imaging biomarkers can be used as a screening, diagnostic or prognostic tool as well as for monitoring treatment response. Researchers have a vision that the introduction of imaging biomarkers will revolutionize basic research, drug development and treatment by providing non-invasive approaches that are translatable from the laboratory to the clinic and by allowing researchers and clinicians to see in great detail how drugs are behaving. The discovery and development of imaging biomarkers is an exciting and growing area and researchers across the globe are working to develop this vision. The imaging technologies available today offer a variety of methods that can be used to quantify information and thus create useful biomarkers. Discovering the biomarker is perhaps the easy step, whilst the clinical follow up studies required to gain a better understanding of the utility of the biomarker are more complex, time consuming and expensive. This report discusses advances in key technologies, the use of imaging biomarkers in drug discovery and development and current use in clinical practice. It also outlines key collaborative initiatives in standardizing imaging technologies and informatics, improving quantification and qualification without which the vision will not be realized. | |
| Keywords: Biomarkers, imaging biomarkers, molecular imaging, biomarker qualification, imaging standards, Magnetic resonance imaging, positron emission tomography | |
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By Dr Cheryl L Barton & Dr Sara Sleigh / Publication Date: 12th July 2010
Contents:
Advances in Imaging Biomarkers
Executive summary 10
Introduction 10
Imaging biomarkers: discovery, development & supporting technologies 11
R&D applications of imaging biomarkers 12
Clinical applications of imaging biomarkers 13
Informatics supporting the clinical application of imaging biomarkers 14
Imaging centers 15
Validation, qualification and regulation of imaging biomarkers 16
The future of the imaging biomarker market 17
Chapter 1 Introduction 20
Summary 20
Introduction 21
Overview of imaging modalities 21
Imaging biomarkers in research and clinical practice 26
Prognostic imaging biomarkers 28
Imaging biomarkers of response 28
Imaging biomarkers of efficacy and dosing 29
Imaging biomarkers of safety 30
Therapeutic areas 30
Importance of imaging biomarkers 30
Report outline 32
Chapter 2 Imaging biomarkers: discovery,
development & supporting
technologies 34
Summary 34
Discovering and developing new imaging biomarkers 35
Advances in imaging technologies and molecular probes 37
Molecular imaging probes 38
NIH-sponsored projects driving molecular imaging 39
Accessibility of molecular imaging probes for PET imaging 40
Combined imaging modalities 42
Technical advances in the field of MRI 43
High field MRI 43
Functional MRI 43
Magnetic resonance spectroscopy 44
Diffusion weighted MRI 45
Targeted probes for MRI 46
Improving MRI resolution with hyperpolarization 46
Spectral CT 50
Advances in optical imaging 51
Photoacoustic imaging 51
Conclusions 52
Chapter 3 R&D applications of imaging
biomarkers 54
Summary 54
Introduction 55
Imaging biomarkers in drug discovery 56
Imaging biomarkers in preclinical development 57
Molecular imaging in preclinical development 58
Imaging toxicity in the preclinical setting 60
Preclinical optical imaging 61
Imaging biomarkers in clinical drug development 61
Imaging biomarkers in Phase 0 clinical studies 62
Imaging biomarkers in Phase I and II clinical trials 63
Imaging in late stage clinical trials 64
Imaging in clinical studies in oncology 65
Imaging biomarkers in clinical studies of CNS therapeutics 65
Imaging in cardiovascular clinical trials 66
Pharma’s imaging centers 67
Case study: the GlaxoSmithKline Clinical Imaging Centre 67
Case study: imaging biomarker development at AstraZeneca 68
Contract research organizations for imaging clinical trials 68
The Society for Nuclear Medicine’s Clinical Trials Network 69
Pre-competitive consortia developing imaging biomarkers 70
The Biomarkers Consortium 71
Conclusion 74
Chapter 4 Clinical applications of imaging
biomarkers 78
Summary 78
Introduction 79
Imaging biomarkers in clinical practice: oncology 81
Breast cancer screening with mammography 81
Established imaging biomarkers for oncology 82
Molecular imaging biomarkers for cancer diagnosis, prognosis and treatment
monitoring 83
Molecular imaging for HER-2 screening and treatment response 87
18F-HX4 (Siemens) 88
18F-ML-10 (Aposense) 89
Cell>Point imaging biomarkers for SPECT 91
Collaborative efforts to develop novel imaging biomarkers at the
Centre for Translational Molecular Medicine 92
Case study: the Cancer Imaging Program, National Cancer Institute 93
Future growth in MRI-based diagnostic imaging biomarkers 94
Imaging biomarkers in clinical practice: neurology 95
Imaging biomarkers for Alzheimer’s disease diagnosis and treatment
monitoring 96
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) 96
Commercial PET ligands in development for AD diagnosis 98
Imaging biomarkers for Parkinson’s disease 102
Imaging biomarkers in clinical practice: cardiovascular disease 104
AdreView (123I-Iobenguane); GE Healthcare 106
KI-0002: Kereos 108
BMS747158; Lantheus Medical Imaging 109
CardioPET, BFPET and VasoPET; FluoroPharma 110
ThromboView (Agen Biomedical) 112
Imaging biomarkers in clinical practice: metabolic disorders 113
Conclusion 113
Chapter 5 Informatics supporting the clinical
application of imaging
biomarkers 116
Summary 116
Software innovation improving the discovery of imaging biomarkers 117
Pattern recognition and image analysis 117
Management of digital images 120
Medical imaging informatics and networking 120
Teleradiology 121
Conclusion 122
Chapter 6 Imaging centers 126
Summary 126
Imaging centers 127
Imaging in the US 128
Quality 129
Appropriateness 129
Reimbursement 130
Imaging in the UK 131
Imaging in India 134
Accessibility of radiopharmaceuticals 135
PET 135
SPECT 136
Conclusions 137
Chapter 7 Validation, qualification and
regulation of imaging biomarkers 140
Summary 140
Introduction 141
Image quantification and standards 143
The Quantitative Imaging Biomarkers Alliance 144
Imaging biomarker qualification 146
Drug-diagnostic co-development 150
Regulatory guidelines for developing novel molecular imaging agents 150
Case study: 18F-labeled sodium fluoride 152
Conclusions 153
Chapter 8 The future of the imaging
biomarker market 156
Summary 156
Introduction 157
Trends in the use of imaging biomarkers in R&D 158
Imaging clinical trials in drug development 158
Saving costs 161
The future: imaging biomarkers and companion diagnostics 162
Trends in the clinical use of imaging biomarkers 164
Prevention and prediction 164
Radiation exposure 165
Costs and reimbursement 167
Imaging biomarker market 170
Overall conclusion 174
Appendices 175
Primary research methodology 175
Glossary 175
Acknowledgements 181
Index 182
Bibliography & Endnotes 184
List of Tables:
List of Figures
Figure 1.1: Imaging techniques and their uses 22
Figure 1.2: Imaging biomarkers in drug development and clinical care 27
Figure 1.3: Types of biomarker and their uses in drug development and disease management 28
Figure 1.4: The potential of imaging biomarkers 31
Figure 2.5: Examples of imaging biomarkers in oncology 35
Figure 2.6: Steps in biomarker development 36
Figure 2.7: Functional magnetic resonance imaging of the brain 44
Figure 2.8: Diffusion MRI - CNS 46
Figure 2.9: Images of the lungs with conventional MRI and hyperpolarized gas MRI 48
Figure 2.10: Schematic of Spectral CT technology 50
Figure 3.11: Pharma industry productivity decline, 2000-2009 55
Figure 3.12: Uses of imaging in preclinical drug development 59
Figure 3.13: Areas of interest for the Society for Nuclear Medicine’s Clinical Trials Network 70
Figure 3.14: The ‘learn and confirm’ model of drug discovery and development 74
Figure 4.15: Imaging modalities for biomarker detection in oncology, neurology and cardiology 80
Figure 4.16: Chemical structure of 18F-ML-10 (Aposense) 89
Figure 4.17: Structures of PET ligands for Alzheimer’s disease diagnosis 100
Figure 4.18: Structures of norepinephrine and AdreView 106
Figure 4.19: Results of the primary endpoint in the ADMIRE-HF study of AdreView (GE
Healthcare) 108
Figure 4.20: Kereos’ targeted nanoparticles 109
Figure 4.21: PET images obtained during the Phase I study of CardioPET (FluoroPharma) 112
Figure 6.22: Impact analysis of the CMS 2010 Physician Fee Schedule Final Rule Summary on
global imaging payments 131
Figure 6.23: CT, MRI and radio-isotope procedures carried out in the UK annually 132
Figure 6.24: Locations of static PET scanners in the UK 133
Figure 6.25: Commercial delivery of 18FDG in the British Isles 134
Figure 7.26: Evolution of biomarkers: towards clinical utility 142
Figure 7.27: Imaging biomarker qualification 146
Figure 7.28: ‘Fit-for-purpose’ qualification of biomarkers 147
Figure 7.29: Pilot biomarker qualification process 149
Figure 8.30: Key stakeholders in the development and use of imaging biomarkers 157