Table Of ContentCANCER THERANOSTICS
CANCER
THERANOSTICS
Edited by
X C
IAOYUAN HEN
S W
TEPHEN ONG
AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON
NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO
SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO
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Preface
Theterm“theranostics”hasbeenusedbymanydifferent optical imaging-guided cancer diagnosis and treatment.
peopleinavarietyofcontexts.Overthepastdecade,the Chapter 6 provides a concise review of optical biolumi-
field of theranostics has evolved considerably and has nescenceimaging in the preclinicalevaluation of tumors
seen spectacular advances in biomarker identification, in response to various cancer therapies. Chapter 7
newmolecularimagingprobesandtechniques,imaging highlightsthe role of magnetic resonanceimaging (MRI)
guided molecular therapy, and novel nanotheranostics. in clinical and experimental oncology to characterize
Thefieldisripetotransformmedicineasawholeanda tumor structure, cell density, blood volume/flow, vessel
greater dissemination of this knowledge can only speed permeability, viable/necrotic components, and meta-
itsrateofacceptanceandimprovement.Newphysicians, bolic changes. Chapter 8 exploits the potential of
researchers,andstudentsworkinginthismultidisciplin- ultrasound imaging at morphological, functional and
ary field often ask how to blend in vitro diagnostics, molecular levels for cancer treatment response assess-
in vivo imaging and therapy together for personalized ment. Chapter 9 discusses the recent development of
medicine,andexpressthedesiretohaveanauthoritative photoacoustic imaging (PAI) to provide functional and
textbook. This textbook, the first of its kind, is designed molecular information about tumor tissue and the
specifically to meet that demand, and is published in applicationsofPAIincancertherapies.
time to meet the needs of medical researchers in a com- Part III (Imaging-Guided Therapy) is composed of
prehensive manner encompassing diagnostics, in vivo Chapters 10(cid:1)13 and describes how advanced imaging
imaging and its use for image-guided therapy, and a techniques now make highly precise surgical interven-
variety of other miscellaneous subjects. To accomplish tion possible. Chapter 10 reveals how the recent
this daunting task we had the good fortune to recruit advancement of image-guided intervention techniques
nearly 60 leaders in the field worldwide contributing to allows real-time visualization of the device and patient
thetwenty-sixchapters. anatomy for efficient, accurate, and safe intervention
Given the multidisciplinary nature of the field, procedures. Chapter 11 describes the emerging coher-
the book is broken into five different sections. Part I ent anti-Stokes Raman scattering (CARS) imaging tech-
(In vitro Diagnostics) consists of three chapters. Many nique that combines label-free molecular vibrational
theranostic approaches for cancer are based on analy- imaging and automated image quantitation for intrao-
sis of tumor biopsy samples removed from the patient perative characterization of cancer lesions. Chapter 12
and analyzed in a laboratory setting. Chapter 1 defines reviews oncologic application of multimodality image-
the term “theranostics” and provides an overview of guided treatment (MIGT) in theory and in practice.
the specific aspects of cancer theranostics. Chapter 2 Chapter 13 introduces medical robotics for cellular and
reviews the advanced biotechnology and computa- molecular imagingof cancer.
tional biology efforts necessary to identify novel Part IV (Theranostic Platforms) consists of Chapters
genomic biomarkers needed for developing targeted 14(cid:1)22.Theultimateapplicationoftheranosticsistodiag-
imaging probes and therapeutics. Chapter 3 describes nose, treat, and monitor a local disorder using a single
the application of bioinformatics methods to discover platform. Chapter 14 discusses the application of light
proteomic biomarkers that are helpful for early tumor inmedicineandtheroleofporphyrinsinphotonicdiag-
diagnosis,prognosis, and treatment. nosticsandinterventions,aswellasapplicationsbeyond
Part II (Molecular Imaging) consists of Chapters 4(cid:1)9. photonicsandstrategiesforimprovingtheirutilizationin
Numerous advances have been made in recent years in oncology. Chapter 15 addresses the fundamental design
exogenousprobesthatallowpreciseandspecificimaging and characteristics of magnetic nanoparticles and their
of cancer in situ as well as label-free clinical imaging attributesinmagneticresonanceimagingandalternating
approaches. Chapter 4 summarizes the major radionu- magnetic fields. Chapter 16 emphasizes the potential of
clide imaging procedures employed in assessing treat- ultrasound-mediated drug and gene delivery strategies
mentresponseinpatientswithcancer.Chapter5focuses as a means of controlled release of therapeutic cargos
on the design of near-infrared fluorescent probes for byeitheracousticcavitationorhyperthermia.Chapter17
ix
x
PREFACE
introduces imaging and therapeutic radionuclides as corresponding pilot plants of nanoparticle production.
well as respective radiopharmaceutical agents used Chapter 25 provides an overview of commercialization
internally in nuclear medicine. Chapter 18 summarizes of nanotechnology, nanomedicine, and theranostic
the basic properties of gold-based nanoparticles and nanomedicine (nanotheranostics) as a foundation for
highlightstheirrecentadvancesasmultifunctionalplat- understanding the challenges of bringing theranostics
forms in cancer theranostics. Chapter 19 summarizes to market. Chapter 26 introduces the origins of cell
the unique physical, chemical, and mechanical charac- heterogeneity in cancer and discusses how this emerg-
teristics of carbon nanomaterials for multimodality ing knowledge has shed light on the difficulties
imaging, photothermal therapy and drug/gene deli- encountered in the management of neoplasias over the
very. Chapter 20 presents some of the recent advances past few decades.
in the development of silica nanoparticle based It is impossible to describe all the areas that thera-
co-delivery of therapeutic and imaging contrast agents. nostics has had, or will have, an impact on the science
Chapter 21 explores the design, synthesis, and applica- and practice of personalized medicine. It is not our
tion of photoluminescent semiconductor nanocrystals, aimtooffer upacompletesolutiontocombinedcancer
or quantum dots (QDs) for traceable therapeutic deli- diagnosis and therapy, but to give readers a sense
very using optical imaging. Chapter 22 reviews the of the opportunities and challenges in this relatively
developmentofpolymer-andprotein-basednanoparti- new field. It has been a great pleasure working with
cle platforms for theranostic applications and discusses the authors of this book. Without their enthusiasm,
the opportunities and challenges that the clinical trans- encouragement and professional delivery of their
lationofsuchnanoparticleplatformsmayencounter. contributions in a timely manner, it would not have
Part V (Other) consists of Chapter 23(cid:1)26 and covers been possible to make this book a reality. Although
a number of informative topics that were too impor- this book focuses on cancer theranostics, many of the
tant to be left out. Chapter 23 is an overview of the concepts and principles described are applicable to
regulatory aspects of cancer theranostics and discusses other disease types. We hope that this book may form
theethicsofhumansubjectprotection andFDAreview a foundation for further advances in the field of
of investigational drugs and devices as they relate to theranostics.
theranostics. Chapter 24 summarizes the current
preparation processes of various theranostic nano- Xiaoyuan (Shawn)Chen, PhD
particles at a lab scale, the scaling-up methods, and Stephen T.C. Wong, PhD, PE
Acknowledgments
Both editors are grateful to their institutions and for her tremendous efforts in helping us assemble this
departments for the continuing support that enabled book, freelance Project Manager Melissa Read for the
this work. We truly appreciate the excellent contribu- production of this book, as well as other talented staff
tions of more than sixty scientists and clinicians who at Elsevier throughout the planning and writing.
sacrificed much of their precious time to the creation Organizing and editing this book volume was pri-
of this book. It is really our great fortune for us to be marily done out of our normal working hours, which
ableto lend the expertiseof a teamof international lea- had an enormous impact on family time. Both editors
ders of their fields. are indebted to their wives and children and thank
Special thanks to Consulting Publisher Wayne them for their support, constant encouragement, and
Yuhasz for his kind invitation to edit this book, patience.
Associate Acquisitions Editor Catherine Van Der Laan
xi
About the Editors
Dr. Xiaoyuan (Shawn) Chen is a Senior Investigator Dr. Stephen Wong is the Founding Chair for
and Chief of the Laboratory of Molecular Imaging and Department of Systems Medicine and Bioengineering,
Nanomedicine (LOMIN) at the National Institute of Houston Methodist Research Institute (HRMI). He
Biomedical Imaging and Bioengineering (NIBIB), holds the John S. Dunn Distinguished Endowed Chair
National Institutes of Health (NIH). His current in Biomedical Engineering. He is a Professor of
research interests include development of molecular Radiology, Neurosciences, Pathology and Laboratory
imaging toolbox for better understanding of biology, Medicine at Weill Cornell Medical College; Director of
early diagnosis of disease, monitoring therapy Translational Research at Methodist Cancer Center,
response, and guiding drug discovery/development. Chief of Medical Physics and Chief Research
His lab puts special emphasis on high-sensitivity nano- Information Officer at Houston Methodist Hospital. He
sensors for biomarker detection and theranostic nano- also serves as the Director of the Chao Center for
medicine for imaging, gene and drug delivery, and BRAIN and of the NCI Center for Modeling Cancer
monitoring of treatment. He received his BS (1993) Development at HMRI. Dr. Wong has over 25 years of
and MS (1996) in chemistry from Nanjing University experienceinacademiaandindustry,includingHewlett
and PhD (1999) in chemistry from the University of Packard, AT&T Bell Labs, Philips Medical Systems,
Idaho. Dr. Chen has published over 400 peer-reviewed Charles Schwab, UCSF, Harvard Medical School and
papers (H-index574, total citations.20,000, over 50 made original contributions in medical imaging, bio-
papers with IF$10) and numerous books and book medicalinformatics,drugrepositioning,andelectronics.
chapters. He is the founding editor of journal He has published over 400 peer-reviewed papers. He
Theranostics (2012 IF57.8). receivedhisBEnginElectricalEngineeringwithhonors
fromtheUniversityofWesternAustralia,MScandPhD
in Computer Science from Lehigh University, and
senior executive education from Stanford University,
Columbia University, and MIT. He is a licensed profes-
sionalengineer.
xiii
List of Contributors
Archie A. Alexander James K. Elrod Department of Health Gi Hyun Choi Department of Maxillofacial Biomedical
Administration, Louisiana State University, Shreveport, Engineering & Institute of Oral Biology, School of
Louisiana,U.S.A. Dentistry,KyungHeeUniversity,Seoul,RepublicofKorea
Miguel Valdivia y Alvarado Houston Methodist Research Mary K. Clancy Office of Research Protection, Methodist
Institute,WeillCornellMedicalCollege,Texas,U.S.A. HospitalResearchInstitute,Houston,Texas,U.S.A.
Emma L.B. Anquillare Laboratory of Nanomedicine and Stanislav Y. Emelianov Department of Biomedical
Biomaterials, Department of Anesthesiology, Brigham and Engineering, University of Texas at Austin, Austin, Texas,
Women’sHospital,HarvardMedicalSchool,Boston,U.S.A. U.S.A;DepartmentofElectricalandComputerEngineering,
UniversityofTexasatAustin,Austin,Texas,U.S.A.
Tobias Ba¨uerle Department of Medical Physics in
Radiology, German Cancer Research Center, Heidelberg, Omid C. Farokhzad Laboratory of Nanomedicine and
Germany; University Hospital Erlangen, Institute of Biomaterials, Department of Anesthesiology, Brigham and
Radiology,Maximiliansplatz1,91054Erlangen,Germany Women’sHospital,HarvardMedicalSchool,Boston,U.S.A.
Weibo Cai Department of Radiology, University of Liang Gao Chroma Technology Corporation, Bellows Falls,
Wisconsin(cid:1)Madison, Madison, Wisconsin, U.S.A; Vermont,U.S.A.
DepartmentofMedicalPhysics,UniversityofWisconsin(cid:1) Tiancheng He Houston Methodist Research Institute, Weill
Madison, Madison, Wisconsin, U.S.A; University of CornellMedicalCollege,Texas,U.S.A.
Wisconsin Carbone Cancer Center, Madison, Wisconsin, Dong Nyoung Heo Department of Maxillofacial Biomedical
U.S.A. Engineering & Institute of Oral Biology, School of
WarrenC.W.Chan InstituteofBiomaterialsandBiomedical Dentistry,KyungHeeUniversity,Seoul,RepublicofKorea
Engineering, University of Toronto, Toronto, Canada; Marshall E. Hicks University of Texas M.D. Anderson
Donnelly Centre for Cellular and Biomedical Research, CancerCenter,Houston,Texas,U.S.A.
Department of Chemical Engineering, Department of
Don N. Ho Laboratory of Molecular Imaging and
Chemistry, Department of Materials Science and
Nanomedicine, National Institute of Biomedical Imaging
Engineering,UniversityofToronto,Toronto,Canada
andBioengineering,NationalInstitutesofHealth,Bethesda,
Tou Pin Chang The Hamlyn Centre for Robotic Surgery, Maryland,U.S.A.
ImperialCollege,London,U.K.
Kurt B. Hodges Department of Basic Medical Sciences and
Chin-Tu Chen Department of Radiology, University of Center for Cancer Research, Purdue University, West
Chicago,Chicago,Illinois,U.S.A. Lafayette, Indiana, U.S.A; Department of Pathology and
FengChen TheragnosticLaboratory,DepartmentofImaging Laboratory Medicine, Indiana University School of
and Pathology, University Hospital, University of Leuven, Medicine,Indianapolis,Indiana,U.S.A.
Leuven,Belgium;DepartmentofRadiology,FirstAffiliated Shao-Ling Huang Division of Cardiology, Department of
Hospital,ZhejiangUniversityHangzhou,Zhejiang,China Internal Medicine, University of Texas at Houston
Jingyi Chen Department of Chemistry and Biochemistry, Medical School, and Center for Clinical and Translational
UniversityofArkansas,Fayetteville,Arkansas,U.S.A. Sciences, University of Texas Health Science Center at
Houston,Houston,Texas,U.S.A.
Nai-Tzu Chen Division of Medical Engineering Research,
NationalHealthResearchInstitutes,ZhunanTown,Miaoli Elizabeth Huynh Ontario Cancer Institute and Techna
County,Taiwan Institute, UHN, Toronto, Canada; Department of Medical
Biophysics,UniversityofToronto,Toronto,Canada
Xiaoyuan Chen Laboratory of Molecular Imaging and
Nanomedicine, National Institute of Biomedical Imaging Hossein Jadvar KeckSchoolofMedicineofUSC,University
andBioengineering,NationalInstitutesofHealth,Bethesda, ofSouthernCalifornia,LosAngeles,California,U.S.A.
Maryland,U.S.A. Guangxu Jin Department of Systems Medicine and
Bioengineering, The Methodist Hospital Research Institute,
Yun-Sheng Chen Department of Biomedical Engineering,
WeillCornellMedicalCollege,Houston,Texas,U.S.A.
University of Texas at Austin, Austin, Texas, U.S.A;
Department of Electrical and Computer Engineering, Fabrice Jotterand Institute of Biomedical Ethics, University
UniversityofTexasatAustin,Austin,Texas,U.S.A. ofBasel,Switzerland
Shih-HsunCheng DivisionofMedicalEngineeringResearch, Dorde Komljenovic Department of Medical Physics in
National Health Research Institutes, Zhunan Town, Miaoli Radiology, German Cancer Research Center, Heidelberg,
County,Taiwan Germany
xv
xvi
LISTOFCONTRIBUTORS
Il Keun Kwon Department of Maxillofacial Biomedical Thillai V. Sekar Molecular Imaging Program at Stanford,
Engineering & Institute of Oral Biology, School of Bio-X Program, Stanford University School of Medicine,
Dentistry, Kyung Hee University, Seoul, Republic of Stanford,California,U.S.A.
Korea Jinjun Shi Laboratory of Nanomedicine and Biomaterials,
Sang Cheon Lee Department of Maxillofacial Biomedical Department of Anesthesiology, Brigham and Women’s
Engineering & Institute of Oral Biology, School of Hospital,HarvardMedicalSchool,Boston,U.S.A.
Dentistry,KyungHeeUniversity,Seoul,RepublicofKorea Jeffrey S. Souris Department of Radiology, University of
Sophie A. Lelie`vre Department of Basic Medical Sciences Chicago,Chicago,Illinois,U.S.A.
and Center for Cancer Research, Purdue University, West Hongying Su Department of Chemical Engineering,
Lafayette,Indiana,U.S.A. Kunming University of Science and Technology,
Fuhai Li Department of Systems Medicine and Kunming, China; State Key Laboratory of Molecular
Bioengineering, Houston Methodist Hospital Research Vaccinology and Molecular Diagnostics & Center for
Institute, Weill Cornell Medical College, Houston, Texas, Molecular Imaging and Translational Medicine, School of
U.S.A. PublicHealth,XiamenUniversity,Xiamen,China
Gang Liu State Key Laboratory of Molecular Vaccinology Pierre-Alexandre Vidi Department of Basic Medical
and Molecular Diagnostics & Center for Molecular Sciences and Center for Cancer Research, Purdue
Imaging and Translational Medicine, School of Public University,WestLafayette,Indiana,U.S.A.
Health, Xiamen University, Xiamen, China; Sichuan Key Carl D. Walkey Institute of Biomaterials and Biomedical
Laboratory of Medical Imaging, North Sichuan Medical Engineering,UniversityofToronto,Toronto,Canada
College,Nanchong,China
Zhantong Wang State Key Laboratory of Molecular
TracyW.Liu OntarioCancerInstituteandTechnaInstitute,
Vaccinology and Molecular Diagnostics & Center for
UHN, Toronto, Canada; Department of Medical
Molecular Imaging and Translational Medicine, School of
Biophysics,UniversityofToronto,Toronto,Canada
PublicHealth,XiamenUniversity,Xiamen,China
Leu-Wei Lo Division of Medical Engineering Research,
Franklin C. Wong University of Texas M.D. Anderson
NationalHealthResearchInstitutes,ZhunanTown,Miaoli
CancerCenter,Houston,Texas,U.S.A.
County,Taiwan
Stephen T.C. Wong Department of Systems Medicine and
Kongkuo Lu Philips Research North America, New York,
Bioengineering, Houston Methodist Hospital Research
U.S.A.
Institute, Weill Cornell Medical College, Houston, Texas,
Thomas D. MacDonald Department of Pharmaceutical U.S.A.
Sciences, University of Toronto, Toronto, Canada; Ontario Zhong Xue Houston Methodist Research Institute, Weill
CancerInstituteandTechnaInstitute,UHN,Toronto,Canada
CornellMedicalCollege,Texas,U.S.A.
James J. Mancuso Department of Systems Medicine and Sheng Xu National Institutes of Health, Bethesda,
Bioengineering, Houston Methodist Hospital Research Maryland,U.S.A.
Institute, Weill Cornell Medical College, Houston, Texas,
Guang-Zhong Yang The Hamlyn Centre for Robotic
U.S.A.
Surgery,ImperialCollegeLondon,U.K.
David D. McPherson Division of Cardiology, Department
Doug Yeager Department of Biomedical Engineering,
of Internal Medicine, University of Texas at Houston
UniversityofTexasatAustin,Austin,Texas,U.S.A.
Medical School, and Center for Clinical and Translational
Sciences, University of Texas Health Science Center at Zheng Yin Department of Systems Medicine and
Houston,Houston,Texas,U.S.A. Bioengineering, Houston Methodist Hospital Research
Institute, Weill Cornell Medical College, Houston, Texas,
Kung Hyun Min Department of Life and Nanopharma-
U.S.A.
ceutical Science, Kyung Hee University, Seoul, Republic
ofKorea Yin Zhang Department of Medical Physics, University of
Wisconsin(cid:1)Madison,Madison,Wisconsin,U.S.A.
Tapas R. Nayak Department of Radiology, University of
Wisconsin(cid:1)Madison,Madison,Wisconsin,U.S.A. Gang Zheng Department of Pharmaceutical Sciences,
University of Toronto, Toronto, Canada; Ontario
Yicheng Ni Theragnostic Laboratory, Department of
Cancer Institute and Techna Institute, UHN, Toronto,
Imaging and Pathology, University Hospital, KU Leuven,
Canada; Department of Pharmaceutical Sciences,
Leuven,Belgium
University of Toronto, Toronto, Canada
Kinam Park Department of Maxillofacial Biomedical
Xi Zhu Laboratory of Nanomedicine and Biomaterials,
Engineering & Institute of Oral Biology, School of
Department of Anesthesiology, Brigham and Women’s
Dentistry,KyungHeeUniversity,Seoul,RepublicofKorea
Hospital, Harvard Medical School, Boston, U.S.A; Key
Ramasamy Paulmurugan Molecular Imaging Program at Laboratory of Drug Targeting and Drug Delivery System,
Stanford, Bio-X Program, Stanford University School of Ministry of Education, West China School of Pharmacy,
Medicine,Stanford,California,U.S.A. SichuanUniversity,Chengdu,Sichuan,China
C H A P T E R
1
Cancer Theranostics: An Introduction
(cid:1) †
Xiaoyuan Chen and Stephen T.C. Wong
(cid:1)
Laboratory of Molecular Imagingand Nanomedicine, NationalInstitute of Biomedical
Imaging andBioengineering, NationalInstitutes ofHealth,Bethesda, Maryland, U.S.A.
†Department of Systems Medicine and Bioengineering,Houston Methodist Hospital ResearchInstitute,
Weill CornellMedical College, Houston,Texas, U.S.A.
O U T L I N E
CancerTheranostics:ADefinition 3 TheranosticPlatforms 5
Theranostic CancerBiomarkers 4 Challenges and Future Perspectives 7
Molecular Imaging inCancerTheranostics 4 References 7
Imaging-Guided Cancer Therapy 5
CANCERTHERANOSTICS: and 21 items for “theragnostics.” In the past two years,
A DEFINITION literaturerelatedtotheranosticsgrewexponentially.As
of October 18, 2013, a PubMed search found 587 items
Theranostics is a portmanteau of therapeutics and for “theranostic,” 562 items for “theranostics,” 85 items
diagnostics. It can be diagnosis followed by therapy to for“theragnostic,”and48itemsfor“theragnostics.”
stratify patients who will likely respond to a given There are pieces of information related to theranos-
treatment. It can also be therapy followed by diagnosis tics in the literature. A dedicated journal named
to monitor early response to treatment and predict Theranostics (www.thno.org/) was launched to open up a
treatment efficacy. It is also possible that diagnostics forum to exchange clinical and scientific information
and therapeutics are codeveloped. For example, nano- for the diagnostic and therapeutic molecular and nano-
platforms can be designed to codeliver imaging and medicine community and allied professions involved
therapy components; antibodies can be labeled for in the efforts of integrating molecular imaging and
imaging and conjugated with payload as antibody- molecular therapy [1]. As an evolving multidisciplin-
drugconjugate(ADC)fortherapy.Cancertheranostics, ary field catering to the unmet needs of the medical
as the name implies, represents a combinatorial diag- world, cancer theranostics include but are not limited
nosis and therapeutic approach to cancer disease and to the following:
aims to reduce delays in treatment and ease patient
care, and appears to be essential for personalized can- (cid:129) Identification of novel biomarkersto advance
certreatment. molecular diagnostics of cancer
Note that in some cases theranostics is also spelled (cid:129) New molecular imaging probesand techniquesfor
as theragnostics. A keyword search of PubMed on early detection of cancer
January7,2011,rightbeforethelaunchofnewSCIjour- (cid:129) Molecular imagingguided cancer therapy
nal Theranostics, only found 95 items for “theranostic,” (cid:129) Nanoplatforms incorporating bothcancerimaging
63 items for “theranostics,” 29 items for “theragnostic,” and therapeuticcomponents
X.ChenandS.Wong(Eds):CancerTheranostics.
DOI:http://dx.doi.org/10.1016/B978-0-12-407722-5.00001-3 3 ©2014ElsevierInc.Allrightsreserved.
