Translational Research in Biophotonics: Four National Cancer Institute Case Studies

364 Pages·2014·29.741 MB·English

by  Robert J. Nordstrom

SPIE PRESS
Bellingham, Washington USA
Library of Congress Cataloging-in-Publication Data
Translational research in biophotonics : four National Cancer Institute case
studies / Robert J. Nordstrom, editor.
pages cm
Includes bibliographical references and index.
ISBN 978-1-62841-068-6 (print : alk. paper) – ISBN 978-1-62841-069-3
(epub) – ISBN 978-1-62841-070-9 (pdf) 1. Diagnostic imaging–Research. 2.
Photonics. 3. Imaging systems in medicine. 4. Imaging systems in biology. I.
Nordstrom, Robert J. (Robert James), 1947- editor of compilation.
RC78.7.D53T735 2014
616.07'54–dc23
2013050195
Published by
SPIE
P.O. Box 10
Bellingham, Washington 98227-0010 USA
Phone: [phone]
Fax: [phone]
Email: [email protected]
Web: http://spie.org
Chapters 3 and 5–9:
Copyright © 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)
Allrightsreserved.Chapters 3and5–9ofthispublication maynotbereproducedor
distributedinanyformorbyanymeanswithoutwrittenpermissionofthepublisher.
The Preface, Chapters 1, 2, and 4, and the Appendix of this book are works of the
U.S. Government and are not subject to copyright.
Thecontentofthisbookreflectstheworkandthoughtoftheauthorsandeditor.Every
effort has been made to publish reliable and accurate information herein, but the
publisher is not responsible for the validity of the information or for any outcomes
resulting from reliance thereon.
Printed in the United States of America.
First printing
Contents
Preface xiii
List of Contributors xvii
List of Acronyms and Abbreviations xxi
1 Introduction to Translational Research 1
Robert J. Nordstrom
1.1 Introduction 1
1.2 Translational Research in Biomedicine 2
1.3 Obstacles Facing Translational Research 7
1.3.1 Academic infrastructure 7
1.3.2 Industrial research efforts 8
1.3.3 Regulatory impediments 9
1.4 The Network for Translational Research (NTR) 9
1.5 Conclusions 10
References 11
2 The NTR: A Format for Translation 13
Pushpa Tandon
2.1 Introduction 13
2.2 Initiation of NTR: Optical Imaging (NTROI) and
Lessons Learned 14
2.3 NTR—Widening the Net: Optical Imaging in Multimodal Platforms 15
2.4 The Four Teams of NTR and the NTR Structure 18
2.4.1 The cross-cutting cores 20
2.4.2 Network governance 22
2.5 Regulatory Approvals: A Critical Step 23
2.6 Lessons Learned 23
2.7 Conclusions 24
References 25
3 Team Sciences and Core Resources within the NTR 29
Melissa B. Aldrich, John C. Rasmussen, Ali Azhdarinia, Bishnu P. Joshi,
Md. Jashim Uddin, Walter J. Akers, Joseph P. Culver, Anne M. Smith,
Jean-Pierre Bouchard, and Katsuo Kurabayashi
v
vi Contents
3.1 Introduction 30
3.2 Validation/Clinical Studies Core 31
3.3 Instrumentation and Industrial Relations Core 38
3.3.1 V&V process during device design 40
3.3.2 Phantoms 42
3.3.2.1 Calibration phantoms 43
3.3.2.2 Development phantom 44
3.3.2.3 Verification phantom 44
3.4 Chemistry Probes and Guided Therapies Core 45
3.5 Center 1: Washington University 45
3.6 Center2:TheUniversityofTexasHealthScienceCenteratHouston 47
3.7 Center 3: University of Michigan 49
3.8 Center 4: Stanford University 50
3.9 Information Technologies Core 52
3.10 Summary 55
3.11 Glossary of Terms 55
Acknowledgments 56
References 56
4 Bringing an Imaging Product into the Clinic 67
Paula M. Jacobs and Dwaine Rieves
4.1 Introduction 67
4.2 Drugs, Devices, and Combinations 70
4.2.1 Drugs 71
4.2.1.1 RDRC 71
4.2.1.2 IND 72
4.2.2 Devices 74
4.2.2.1 Classification 74
4.2.2.2 Investigational device exemptions 75
4.2.3 Combination products 75
4.3 Clinical Trials 76
4.4 Good Manufacturing Practices and Quality System Regulations 76
4.4.1 Manufacturing PET for clinical investigation 77
4.4.2 Basic principles of manufacturing 77
4.5 Preclinical Safety Studies 78
4.6 Summary 79
References 79
5 Clinical Translation of Photoacoustic Tomography 83
Todd N. Erpelding, Konstantin Maslov, Catherine Appleton,
Julie A. Margenthaler, Michael D. Pashley, Jun Zou, Joseph P. Culver,
Walter J. Akers, Samuel Achilefu, Dipanjan Pan, Gregory M. Lanza,
and Lihong V. Wang
5.1 Clinical Problem: Invasiveness of Breast Cancer Staging 84
Contents vii
5.2 Primary Technological Solution 86
5.2.1 Minimally invasive technology 86
5.2.2 Safe and low-cost technology 88
5.3 Clinical Resources Needed and Patient Recruiting 88
5.3.1 First-rate research hospitals and administrative commitment 88
5.3.2 Compatibility with clinical workflow 89
5.4 Clinical Translation 90
5.4.1 PAT-US system 90
5.4.2 Preclinical SLN mapping using PAT-US 91
5.4.3 Clinical SLN mapping using PAT-US 93
5.4.4 Clinical challenges and system improvements 96
5.4.4.1 Clinicalchallenge:Clinicallyacceptablephotoacoustic
transducer 96
5.4.4.2 Clinical challenge: Suitable imaging frame rate 97
5.4.4.3 Clinical challenge: Lack of PAT imaging specificity
for MB dye 97
5.5 Emerging Technological Solutions 100
5.5.1 3D PAT SLN mapping 100
5.5.2 Parallel acoustic delay lines 103
5.5.2.1 Introduction 103
5.5.2.2 Optical-fiber PADLs 105
5.5.2.3 Photoacoustic imaging with optical fiber PADLs 107
5.5.2.4 Micromachined silicon PADLs 110
5.5.3 Molecular imaging 113
5.5.3.1 Handheld video-rate fluorescence DOT hardware 113
5.5.3.2 Demonstration of SLN detection in animal models 114
5.5.3.3 Monomolecularmultimodalimagingagents(MOMIAs)
forphotoacousticandnuclearmedicineimaging 115
5.5.3.4 Fluorescenceimagingwith125I-cypate-Tyrforlymph
nodedetection 117
5.5.3.5 Photoacousticandfluorescenceimagingwith
targetedNIRperfluorocarbonnanoparticles 120
5.5.3.6 SPECT/CT acquisition 122
5.5.4 Nanoparticle contrast agents 125
5.5.4.1 Gold nanobeacons 125
5.5.4.2 Gold rod nanobeacons 128
5.5.4.3 SLN imaging with GNB 130
5.5.4.4 Integrin-specific photoacoustic imaging of
angiogenesis 133
5.5.4.5 Photoacoustic agents incorporating NIR cyanine
dyes for real-time SLN imaging 137
5.5.4.6 Copper as a contrast agent in photoacoustic
imaging of SLNs 139
viii Contents
5.5.4.7 Future prospects for “soft” nanocontrast agents
and photoacoustic tomography 142
5.6 Conclusions 143
References 144
6 Acceleration of Translational Research: Enabling Discovery 159
Eva M. Sevick-Muraca
6.1 Introduction 159
6.2 TheConnectionsbetweenFluorescenceandNuclearImaging
Techniques:ThePhysics,andRegulatoryandTranslationalPathways 161
6.2.1 Nuclear imaging agents 163
6.2.2 NIRF imaging agents 163
6.2.3 Limiting factors: NIRF agent validation 164
6.2.4 Limiting factors: NIR versus far-red and visibly excited
fluorophores 165
6.2.5 Limiting factors: efficient collection of fluorescent light 165
6.2.6 TheregulatorypathwaysfornuclearimagingandNIRFimaging 166
6.3 Discovery in Translational Research 170
6.3.1 The lymphatic vasculature 171
6.4 Standards and Validation in Translational Research 180
6.4.1 Standardization and validation of imaging devices 181
6.4.2 Validated studies of imaging agents 186
6.5 Translating New Technologies to Meet Unmet Clinical Needs 189
Acknowledgments 191
References 192
7 Imaging and Biomarkers for Early Detection of Colorectal Cancer 201
D. Kim Turgeon, Bishnu P. Joshi, Bill R. Reisdorph, and Thomas D. Wang
7.1 Introduction 202
7.2 Describing the Unmet Clinical Need 204
7.2.1 Identifying the clinical problem 204
7.2.2 Explaining the need for new methods 205
7.2.3 Defining the role for imaging 206
7.3 Proposing the Solution 207
7.3.1 Identifying promising imaging targets 207
7.3.2 Matching targets with molecular probe platform 208
7.3.3 Choosing the appropriate imaging modalities 210
7.3.4 Defining the multimodality imaging platforms 212
7.4 Recruiting the Study Team 212
7.4.1 Clinical studies team 213
7.4.2 Regulatory support 213
7.4.3 Industrial partners 214
7.5 Planning to Commercialize the Technology 215
7.5.1 Protecting the intellectual property 215
Contents ix
7.5.2 Managing potential conflicts of interest 215
7.5.3 Centers for Medicare & Medicaid Services 216
7.6 Performing the Preclinical Studies 216
7.6.1 Macroscopic imaging 217
7.6.2 Mesoscopic imaging 217
7.6.3 Microscopic imaging 220
7.7 Developing the Regulatory Strategy 222
7.7.1 Combining the imaging agent with the instrument 223
7.7.2 GMP synthesis of the fluorescent-labeled peptide 224
7.7.3 Performing the pharmacology/toxicology study 225
7.7.4 Obtaining Chemistry, Manufacturing, and Controls (CMC)
documentation 225
7.7.5 Phase I clinical study 226
7.7.6 Submitting the IND application 228
7.7.7 Regulatory approval of the confocal imaging instrument 229
7.8 Performing the Clinical Study 229
7.8.1 Peptide safety in human subjects 229
7.8.2 Data Safety Monitoring Board 230
7.8.3 Retention of clinical records 231
7.9 Commercializing the Product 231
7.9.1 Articulating the technological innovation 231
7.9.2 Envisioning the commercialized product 231
7.9.3 Explaining the clinical value proposition 231
7.9.4 Identifying competing products 232
7.9.5 What are the likely markets? 232
7.9.6 What are the perceived barriers to commercialization? 232
7.10 Conclusions and Future Directions 232
Acknowledgments 233
References 233
8 Using Optics to Reduce the Time and Distance between the Patient
and the Diagnostic Event 243
Stephan Rogalla, Steven Sensarn, Bonnie L. King, Tobi L. Schmidt,
Hyejun Ra, Ellis Garai, David Rimm, David Ostrov, Md. Jashim Uddin,
Lawrence J. Marnett, Cristina Zavaleta, Sanjiv S. Gambhir, James M. Crawford,
Jacques Van Dam, Shai Friedland, Olav Solgaard, Michael Mandella, and
Christopher H. Contag
8.1 Introduction 244
8.2 Clinical Problems to be Solved 245
8.3 Technology Developed to Address Clinical Needs 247
8.3.1 DAC microscope 247
8.3.2 3.8-mm multispectral DAC and MEMS scanning mirrors 248
8.3.3 DAC and wide-field fluorescent system: macro- and
microscopic detection of fluorescent probes 252