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Nano Today (2013) xxx, xxx—xxx

Available online at www.sciencedirect.com

j our na l ho me pag e: www.elsev ier .com/ locate /nanotoday

NEWS AND OPINIONS

Nanoparticles for cancer imaging: The good,the bad, and the promise

Sandra Chapmana,∗, Marina Dobrovolskaiab, Keyvan Farahanic,Andrew Goodwind, Amit Joshie,f, Hakho Leeg, Thomas Meadeh,Martin Pomper i, Krzysztof Ptakj, Jianghong Raok, Ravi Singh l,Srinivas Sridharm, Stephan Sternb, Andrew Wangn,John B. Weavero, Gayle Woloschakp,q,r,∗∗, Lily Yangs

a Office of Cancer Nanotechnology Research, Center for Strategic Scientific Initiatives, National CancerInstitute, NIH, Bethesda, MD 20892, United Statesb Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., Advanced Technology Research Facility— Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, United Statesc Image-Guided Interventions Branch, Cancer Imaging Program, National Cancer Institute, Rockville, MD20852, United Statesd Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80303,United Statese Department of Radiology, TBMM Graduate Program, Baylor College of Medicine, Houston, TX 77030,United Statesf Department of Molecular Physiology and Biophysics, TBMM Graduate Program, Baylor College ofMedicine, Houston, TX 77030, United Statesg Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114,United Statesh Departments of Chemistry, Molecular Biosciences and Radiology, Northwestern University, Evanston, IL60208, United Statesi

Johns Hopkins Medical School, Baltimore, MD 21287, United Statesj Office of Cancer Centers, Office of the Director, NCI, NIH, Bethesda, MD 20892, United Statesk Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA94305-5080, United Statesl Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States m Nanomedicine Science and Technology Center and Department of Physics, Northeastern University,

Please cite this article in press as: S. Chapman, et al., Nano Today (2013),http://dx.doi.org/10.1016/j.nantod.2013.06.001

Boston, MA 02115, United States

∗ Corresponding authors.∗∗ Corresponding author at: Department of Radiology, Robert E. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL

60611, United States.E-mail addresses: chapmansandra.e@gmail.com (S. Chapman), g-woloschak@northwestern.edu (G. Woloschak).

1748-0132/$ — see front matter. Published by Elsevier Ltd.http://dx.doi.org/10.1016/j.nantod.2013.06.001

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2 S. Chapman et al.

n Department of Radiation Oncology, Lineberger Comprehensive Cancer, Carolina Center for NanotechnologyExcellence, University of North Carolina-Chapel Hill, NC 27599, United Stateso Department of Radiology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, United Statesp Department of Radiation Oncology, Robert E. Lurie Comprehensive Cancer Center, Northwestern University,Chicago,IL 60611, United Statesq Department of Radiology, Robert E. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,IL 60611, United Statesr Department of Cell and Molecular Biology, Robert E. Lurie Comprehensive Cancer Center, NorthwesternUniversity, Chicago, IL 60611, United Statess Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, United States

Received 20 February 2013; received in revised form 12 June 2013; accepted 13 June 2013

Summary Recent advances in molecular imaging and nanotechnology are providing new oppor-tunities for biomedical imaging with great promise for the development of novel imaging agents.The unique optical, magnetic, and chemical properties of materials at the scale of nanometersallow the creation of imaging probes with better contrast enhancement, increased sensitiv-ity, controlled biodistribution, better spatial and temporal information, multi-functionality andmulti-modal imaging across MRI, PET, SPECT, and ultrasound. These features could ultimatelytranslate to clinical advantages such as earlier detection, real time assessment of disease pro-gression and personalized medicine. However, several years of investigation into the applicationof these materials to cancer research has revealed challenges that have delayed the successfulapplication of these agents to the field of biomedical imaging. Understanding these challengesis critical to take full advantage of the benefits offered by nano-sized imaging agents. There-fore, this article presents the lessons learned and challenges encountered by a group of leadingresearchers in this field, and suggests ways forward to develop nanoparticle probes for cancer

KEYWORDSNanomedicine;Cancer;Imaging;Detection;Screening

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imaging.Published by Elsevier Ltd.

Recent advances in molecular imaging and nanotech-ology are providing new opportunities for biomedicalmaging with great promise for the development of agentso address clinical needs for disease staging, stratifica-ion, and monitoring of responses to therapy [1]. Materialst the scale of nanometers possess unique optical, mag-etic, and chemical properties which allow the creation ofmaging probes with increased signal density, signal amplifi-ation and quantification, improved contrast, and controllediodistribution.

In 2011, the NCI Office of Cancer Nanotechnol-gy Research (OCNR) assembled an imaging workingroup comprised of researchers working in the field ofanoparticle-based cancer imaging with the task of review-ng the current status of the field and identifying challengesssociated with developing nanoparticle-based cancer imag-ng probes and bringing them into the clinic. In this article,e examine the current issues and challenges associatedith nanotechnology-based imaging, and suggest opportuni-

ies for development of nanoparticle-based cancer imagingodalities.

imitations of current nanoparticle imaging

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robes

n ideal nanoparticle imaging probe for clinical usehould be biodegradable or rapidly excreted and have

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low toxicity while producing a strong imaging signal.everal common issues shared among different nanopar-icles compromise their further transition into clinicalse.

arriers for effective tumor delivery

rior to reaching the tumor target, nanoparticles adminis-ered through intravenous injection interact with a complexnvironment that has evolved to seek out and excludeoreign matter. Primary obstacles to effective delivery ofanoparticles into tumors include clearance by the mono-uclear phagocyte system (MPS) [2] and the heterogeneityf the tumor microenvironment, particularly in regardso physiological barriers such as antigen expression, andascular and tumor permeability, which prevent both accu-ulation of sufficient quantities and uniform delivery ofrugs and nanoparticles to all regions of tumors [3]. Afterntering the blood circulation, nanoparticles often bindlasma proteins (opsonization) and are taken up by phago-ytic cells in the blood, liver, spleen and bone marrow. This

Chapman, et al., Nano Today (2013),

mall fraction available for uptake at the tumor sites; sec-nd, it may lead to long retention times of potentially toxicanoparticle components or metabolites, which presentsignificant concerns of off-target and chronic toxicities.

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Nanoparticles for cancer imaging

The tools available to mitigate these effects are limited.A commonly used approach to reducing MPS clearance andincreasing circulation times is steric stabilization of particledispersions by polyethylene glycol (PEG) coating. Long cir-culation times achieved by PEG-coated ‘‘stealth’’ particlesdo not necessarily lead to enhanced accumulation deep intotumors, and PEG-coating may inhibit uptake of the nanopar-ticles by tumor cells. Current understanding of the effect ofphysicochemical characteristics of most nanoparticle con-structs on their blood circulation times and body clearance islimited to basic parameters such as size and zeta-potential,while the role of other properties (shape, hydrophobic-ity, rigidity, etc.) is less understood. A significant effortis needed to create particles with optimal characteristicsassociated with both tumor specific accumulation and bodyclearance.

Imaging very small tumors

A key advantage of using nanoparticle imaging agents ascompared to small molecules is the opportunity for pref-erential localization at the disease site through enhancedpermeability and retention (EPR). When a tumor reachesa certain size (typically over 1 mm in diameter), its vas-culature becomes leaky and its lymphatic drainage systemis dysfunctional, as well. Nanoparticles with long bloodcirculation times will tend to accumulate in the tumorinterstitial space after moving across the leaky tumorblood vessels. The size of the gap openings of tumor vas-culature is usually in the range of 400—600 nm, whichis much larger than that found in most normal tissues[3,4].

It is generally agreed that targeting ligands facilitate theinternalization of nanoparticles by target cells and increasetheir retention in tumors. However, it is unclear if anynanoparticle-based strategy can enhance detection of thesmallest tumors that do not possess a leaky tumor vascula-ture that favors EPR. Resolving these questions will requireparallel developments in the identification of better target-ing moieties and nanoparticle design.

Immunology

Immunological reactivity is a common toxicity observed withthe clinical use of most contrast agents currently approvedfor diagnostic imaging. In addition to the immune reactiv-ity of the nanoplatform itself, combination with targetingligands, repeated administration, and contamination withendotoxins and pyrogens during the manufacturing process,can further increase the likelihood for immunogenicity [5].

Blood compatibility tests are required for nanoparticlesdistributed within the systemic circulation by the FDA beforeinitiating phase 1 clinical studies. This type of testing isfocused on detecting acute toxicities mediated by particleeffects on erythrocytes (hemolysis), platelets, leukocytesand coagulation factors (thrombogenicity) and complementsystem (anaphylaxis). Nanoparticle interference with tradi-

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tional in vitro tests is a common challenge during this step[5]. Understanding of the correlation between in vitro andin vivo immunotoxicity assays for nanomaterials significantlyaids in conducting preclinical studies [16].

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oxicology

he selective tissue distribution of targeted nanoparticlesnd the accumulation of some nanomaterials within organsf the MPS, both require greater toxicological evaluation.his is especially the case for biopersistant nanomaterials,uch as some metallic particles, that may result in chronicoxicities. Due to delayed clearance and increased systemicirculation relative to conventional imaging agents, theres the potential issue for increased systemic exposure tooxic components of nanomaterial-based imaging agents6,7]. Nanoparticles may form micron-scale aggregates uponnjection into the circulation, leading to microcirculationompromise, particularly in the capillary beds of the lungsnd can result in inflammation and granuloma formation [8].t is important to investigate the aggregation tendency ofntravenous nanoparticles in plasma, especially when agentsre dosed at high particle concentrations, and also to eval-ate the lung as a potential target organ.

urdles on the road to the clinic

linical translation of nanoparticle-based imaging agentsas been very challenging and many obstacles have yet toe overcome. In contrast to therapeutic delivery systems,hich are administered after confirmed diagnosis of disease,

maging agents are often used for diagnostic purposes prioro confirmed diagnosis. Accordingly, the regulatory burdens much greater for imaging than for therapeutic agents inrder to avoid needless toxicity to patients who might turnut to be healthy.

egulatory considerations

hile no new toxicities, specific to nanoparticles, have beeneported [5,9], there is always a concern that the nanometerizes may lead to toxic response even if the nanoparti-le constituents are Food and Drug Administration (FDA)pproved. At present, in order to receive investigationalew drug (IND) or investigational device exemption (IDE)pproval, the U.S. FDA requires similar preclinical data foranoparticle-based therapeutic and imaging agents as forny other new therapeutic or diagnostic [10]. The scope ofafety studies is determined by four main criteria: (1) massose, (2) route of administration, (3) frequency of use, and4) biological, physical and effective half-lives [11]. For anmaging probe, it is necessary to demonstrate specificity andensitivity using a clinically relevant dose, and evaluate initro and in vivo stability, systemic toxicity, and pharmacoki-etics and pharmacodynamics [12].

Unlike small molecule agents, nanoparticle contrastgents usually have complex formulations and multiple com-onents, which make it challenging for the production ofhe nanoparticles in a large scale with consistent qual-ty using Good Manufacturing Practice (GMP). Furthermore,ystemic biodistribution, toxicity, and clearance of eachomponent of the nanoparticle core, surface coating, and

Chapman, et al., Nano Today (2013),

argeting ligand should also be fully examined in appropri-te animal models. To facilitate the regulatory review ofanotechnologies intended for cancer therapies and diag-ostics, the National Cancer Institute (NCI) established the

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anotechnology Characterization Laboratory to performreclinical efficacy and toxicity testing of nanoparticleseveloped by the research community and facilitate theirrogress through the regulatory approval process.

inancial realities

conomic considerations present additional and significanthallenges in translating nanoparticle imaging agents to thelinical setting. The cost-effectiveness of these agents wille critical to their commercialization. In clinical medicine,dditional imaging information frequently does not translatento changes in patient management decisions. Success-ul nanoparticle-based imaging agents will possess clearnd measurable advantages over existing small moleculegents.

A targeted nanoparticle imaging agent that demonstratesarly detection of cancers or detection of micro-metastasesould clearly justify its cost by allowing for early inter-ention. Nanoparticle imaging agents could also providerognostic indicators of early therapeutic effectiveness,llowing physicians to rapidly alter therapeutic strategies,ersonalizing care to the individual patient and improvingverall response.

Another important consideration is the financial incen-ive for the commercialization of molecular imaging agents.lthough the imaging agent market is projected to expando approximately $14 billion by 2015, it is not clearhether nanoparticle agents will be financially beneficial

or companies developing them [13]. Nanoparticle imaginggents face similar cost concerns as nanoparticle thera-eutic agents; R&D costs are inherently high and insurersre becoming more prudent in their re-imbursement poli-ies. Furthermore, due to the existing reimbursementolicies for imaging agents, the incentives involved ineveloping imaging agents are far fewer than those ofherapeutic agents. Poor sales of one nanoformulated ironxide MRI contrast agent, Feridex, and the high barrieror securing regulatory approval for another, Combidex,ave prompted their manufacturer to discontinue theseroducts.

pportunities

ne of the most important advantages of nanoparticlemaging agents is their ability to anchor a large numberf the same or different molecules. The multi-functionalapabilities of nanoparticles can lead to tailor-made imag-ng agents for personalized medicine. Future nanoparticlemaging agents will include capabilities through appropriateunctionalization that will classify tumor subtypes in highlyeterogeneous tumors based on identifying genetic or epi-enetic markers with in vivo and ex vivo diagnostics leadingo personalized therapies.

The ability for multi-functionalization perhaps offers thereatest potential for clinical use by enabling compatibilityn multiple imaging modalities (e.g. MR/CT, MR/PET, optical

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maging, and others) in a single nanoplatform. Multimodalitymaging allows complementary information over differentemporal and spatial scales or different resolution or detec-ion ranges for the same marker acquired from probes that

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ocalize to the same place at the same time; this provides aar more detailed picture than otherwise would be available.here is a widely acknowledged lack of safe MRI contrastgents especially because of concerns over the safety. It isoped that use of nanoconstructs using iron oxide nanoparti-les (some of which are FDA approved) may overcome somef these safety concerns while increasing contrast enhance-ent and imaging efficacy.Theranostic nanoparticles, defined as those that combine

he capacity for tumor imaging with therapeutic efficacy andow toxicity, are a novel concept currently at the preclin-cal stage and may provide the opportunity for real-timemaging of tumors as patients are undergoing therapy. Thebility to monitor early indicators of therapeutic responseould permit adjustment of treatment regimens and per-onalization of care. Biotechnology and pharmaceuticalompanies have expressed a willingness to invest in thera-ostic agents because of their potential for becoming novelnd effective cancer therapeutic agents. However, whilehere are strong scientific rationales and urgent clinicaleeds for developing image-guided and targeted drug deliv-ry agents, regulatory approval of these multi-functionalgents faces greater challenges due to their complex-ty.

Nanotechnology is also driving the development of newools and instruments that may have a broad impact on clin-cal medicine, even if nanotechnology imaging agents mayot make their way into in vivo use. Nanomaterials combinedith imaging are being developed for high throughput diag-ostic assays and improved tumor biopsies. A significant areaf increasing application is in ex vivo diagnostics using imag-ng agents such as quantum dots, where bio-compatibility isot a requirement. Advances in magnetic nanoparticles havelso led to a new imaging modality based on direct detec-ion of particles [14]. Nanomaterials are also being used toevelop new X-ray sources [15].

Overall, nanotechnology offers the promise to revolu-ionize the field of medical imaging. The ability to imagend treat simultaneously, the ability to enhance tumoretection, and the ability to have multiple contrast agentsn a single platform may drastically change patient man-gement. Despite the challenges associated with clinicalranslation that must be overcome, nanotechnology is antic-pated to play a major role in future medical imaging.ecause nanoparticle imaging agents possess many advan-ages over their small molecule counterparts, we anticipateanoparticle molecular imaging agents will ultimately beuccessful in the clinic.

isclaimer

he content of this publication does not necessarily reflecthe views or policies of the Department of Health and Humanervices, nor does mention of trade names, commercialroducts or organizations imply endorsement by the US Gov-rnment.

Chapman, et al., Nano Today (2013),

inancial and competing interests disclosure

his project has been funded in whole or in part with fed-ral funds from the National Cancer Institute (NCI)—NIH

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under contract number HHSN261200800001E. All authors arepart of the NCI Alliance for Nanotechnology in Cancer andhold either Center of Cancer Nanotechnology Excellenceor Cancer Nanotechnology Platform Partnership grants. Theauthors have no other relevant affiliations or financialinvolvement with any organization or entity with a finan-cial interest in or financial conflict with the subject matteror materials discussed in the manuscript apart from thosedisclosed.

No writing assistance was utilized in the production ofthis manuscript.

Acknowledgements

The authors would like to thank J Whitley, Creative Leadfor Instructional Innovation in the Educational TechnologyResearch and Development Group at the UNC EshelmanSchool of Pharmacy, for his creation of Figures 1 & 2.

References

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3 (2008) 703—717.[8] P.P. Adiseshaiah, J.B. Hall, S.E. McNeil, Nanomed.

Nanobiotechnol. 2 (2010) 99—112.[9] S.T. Stern, S.E. McNeil, Toxicol. Sci. 101 (2008) 4—21.

[10] U.S.F.a.D.A. FDA, Fed. Regist. 63 (1998) 55067—55069.[11] U.S.F.a.D. Administration, in: C.f.D.E.a.R.C.a.C.f.B.E.a.R.

CBER (Ed.), Guidance for Industry: Developing Medical ImagingDrug and Biological Products, 2004.

[12] (FDA), U.S.F.a.D.A., Development & Approval Process (Drugs),2012.

[13] Global Industry Analysts, I. Imaging Agents: A Global StrategicBusiness Report, San Jose, CA, 2010.

[14] B. Gleich, J. Weizenecker, Nature 435 (2005) 1214—1217.[15] S. Wang, et al., Appl. Phys. Lett. 98 (2011) 213701.[16] M.A. Dobrovolskaia, S.E. McNeil, Handbook of Immunological

Properties of Engineered Nanomaterials, WorldScientific Pub-lishing Co. Ltd., Singapore, 2013, pp. 752.

Sandra Chapman is an American Associationfor the Advancement of Science (AAAS) Sci-ence and Technology Policy Fellow working asa projects manager for NCI’s Office of CancerNanotechnology Research. Sandra recentlycompleted her graduate studies at Pennsyl-vania State University, College of Medicine,earning her PhD in molecular medicine in July2010. Her thesis research on the human papil-lomavirus life cycle was the product of a

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collaboration between laboratories at Penn-sylvania State University and the National Institutes of Health. Herresearch resulted in publications and is currently under review forpatent approval. She received her bachelor’s degree in economicsfrom the University of California, Santa Barbara. I

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At the NCL, Dr. Dobrovolskaia directs char-acterization related to a nanomaterials’interaction with components of the immunesystem. She monitors acute/adverse effectsof nanoparticles as they relate to the immunesystem, both in vitro and in animal mod-els. Dr. Dobrovolskaia is also responsiblefor the development, validation and perfor-mance qualification of in vitro and ex vivoassays to support preclinical characterizationof nanoparticles, and for monitoring nanopar-

icle purity from biological contaminants such as bacteria, yeast,old and endotoxin. Additionally, she leads structure activity rela-

ionship studies aimed at identifying the relationship betweenanoparticle physicochemical properties and their interaction withacrophages, components of the blood coagulation cascade, and

omplement systems.

Dr. Farahani is a Program Director in theImage-Guided Interventions (IGI) Branch,Cancer Imaging Program, National CancerInstitute. In this capacity he is responsi-ble for the development of NCI initiativesthat address diagnosis and treatment of can-cer through integration of advanced imagingand minimally invasive technologies. Since2002 Dr. Farahani has lead the NCI initiativesin Oncologic IGI focused on small businessdevelopment, early phase clinical trials, and

mage-guided drug delivery systems, including nanotechnologies.e has led a series of NCI workshops that promote an open sci-nce model to develop, optimize and validate platforms for IGI.hese activities have engaged other institutes of the NIH, as wells the FDA, NIST and CMS. Prior to joining NCI in fall of 2001, Dr.arahani was on faculty of the department of Radiological Sciencesn UCLA, where he obtained his PhD (’93) in Biomedical Physics.r. Farahani is a member of the American Association of Physicists

n Medicine, the Scientific Program Committee of the Radiologicalociety of North America, and a past president of the InterventionalR Study Group of the International Society of Magnetic Resonance

n Medicine.

Andrew Goodwin is an Assistant Professorin the Department of Chemical and Biologi-cal Engineering at the University of ColoradoBoulder and a recipient of a K99/R00 Path-way to Independence Award through theNCI Alliance for Cancer Nanotechnology. Hisresearch focuses on designing ‘‘smart’’ col-loids and materials — such as polymericarchitectures, organic/inorganic hybrids, andmultiphase composites — that can sense theirsurroundings and change their physical prop-

rties accordingly. He obtained his PhD in Chemistry from theniversity of California, Berkeley and his BA in Chemistry fromolumbia University in New York.

Amit Joshi is an Assistant Professor in theDepartments of Radiology and Molecular Phys-iology at Baylor College of Medicine, andan adjunct faculty member in Electricaland Computer Engineering at Rice Univer-sity, Houston, Texas. Amit’s research interestsspan across the interface of Nanophotonicsand Biological Systems. Amit is developing

Chapman, et al., Nano Today (2013),

multifunctional nano particle based technolo-gies for simultaneous imaging, and externallytriggered therapy of cancer with Near

nfrared light and Magnetic resonance based methods.

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Hakho Lee, PhD is Assistant Professor in Radi-ology at Harvard Medical School, and AssistantProfessor in Bioengineering at the MGH Centerfor Systems Biology. Prof. Lee studied Physicsat Seoul National University, and receivedhis PhD in Physics from Harvard University,and completed his post-doctoral training atMassachusetts general Hospital. His researchgroup focuses on developing highly sensitive,portable biosensors through multidisciplinaryintegration of nanomaterials, microelectron-

cs and microfluidics. Over the past years, Prof. Lee’s lab hasdvanced magnetic sensing technology by synthesizing new typesf magnetic nanoparticles and implementing chip-based magneticensors.

Thomas Meade, PhD, received a BS in chem-istry, MS in biochemistry and PhD in inorganicchemistry. After completing postdoctoral fel-lowships at Harvard Medical School and theCalifornia Institute of Technology, he joinedthe faculty at Caltech and the Beckman Insti-tute where he pioneered the developmentof the first bioactivated MR probes and thedevelopment of hand-held chips for DNA andprotein diagnostics. In 2002, he moved toNorthwestern University, where he is the

ileen M. Foell Professor of Cancer Research and Professor ofhemistry, Molecular Biosciences, Neurobiology & Physiology, andadiology, as well as the Director of the Center for Advanced Molec-lar Imaging. Professor Meade’s research focuses on bioinorganicoordination chemistry and its application in research that includeiological molecular imaging, transcription factor inhibitors and theevelopment of electronic biosensors for the detection of DNA androteins.

Martin Pomper is the William R. BrodyProfessor of Radiology at Johns Hopkins Uni-versity. He received undergraduate, graduate(organic chemistry) and medical degreesfrom the University of Illinois at Urbana-Champaign. Postgraduate medical trainingwas at Johns Hopkins, including internship onthe Osler Medical Service, residencies in diag-nostic radiology and nuclear medicine anda fellowship in neuroradiology. He is board-certified in diagnostic radiology and nuclear

edicine. He has been on the Radiology faculty at Johns Hopkinsince 1996. His interests are in the development of new radiophar-aceuticals, optical probes and techniques for molecular imaging

f central nervous system disease and cancer.

Dr. Krzysztof Ptak joined the National CancerInstitute Office of Cancer Centers in January2012 as a Program Director. In this capacity,he contributes to the management of CancerCenter Support Grants. Previously, he servedas a Project Manager in the NCI Office of Can-cer Nanotechnology Research.Dr. Ptak holds a PhD in Neuroscience from

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the University of Paul Cezanne in Marseilleand Jagiellonian University in Krakow. He alsoholds an MBA in Life Science from The Carey

usiness School at Johns Hopkins University.

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Dr. Rao received his BS in Chemistry fromPeking University, China, in 1991, a PhD. inChemistry from Harvard University in 1999under the guidance of Professor George M.Whitesides, and a Damon Runyon CancerResearch Foundation postdoctoral fellow-ship at UCSD with Professor Roger Y. Tsien.He began his assistant professorship in theDepartment of Molecular and Medical Phar-macology at UCLA in 2002, and currently anAssociate Professor of Radiology and Chem-

stry at Stanford University. His research interests include molecularrobes, cancer imaging, bionanotechnology, biosensing, and chem-cal biology.

Ravi Singh, PhD is an Assistant Professor ofCancer Biology, Biomedical Engineering andPhysics at Wake Forest School of Medicine.His research interest is the production ofnanotechnology-based, multifunctional par-ticles for cancer diagnosis, therapy, andtreatment monitoring. He earned a BA inphysics from Harvard University then spenteight years conducting research in viral andnon-viral gene therapy at Weill Cornell Med-ical Center and Imperial College London

efore initiating graduate studies at University College Londonhere he earned a PhD in Pharmaceutical Science. Dr. Singh com-leted his post-doctoral training in Cancer Biology at Wake Forestchool of Medicine.

Srinivas Sridhar is Arts and Sciences Distin-guished Professor of Physics at NortheasternUniversity, and Visiting Professor of RadiationOncology, Harvard Medical School. He is theDirector and Principal Investigator of the NSFIGERT Nanomedicine Science and TechnologyCenter. He is the founding Director of theElectronic Materials Research Institute, andformerly served as Vice Provost for Researchat Northeastern University, overseeing theUniversity’s research portfolio. An elected

ellow of the American Physical Society, Sridhar’s current areasf research arenanomedicine and nanophotonics. He has publishedore than 175 journal articles and has made more than 160 presen-

ations worldwide. For more information visit www.igert.neu.edund sagar.physics.neu.edu.

Dr. Stern heads the pharmacology and tox-icology program at the Frederick NationalLaboratory’s Nanotechnology Characteriza-tion Laboratory. Prior to joining the NCL, Dr.Stern was a Post-Doctoral Fellow at the Uni-versity of North Carolina - Chapel Hill in theDivision of Drug Delivery and Disposition, andCurriculum in Toxicology. Dr. Stern’s areas ofexpertise include biochemical toxicology ofthe liver and kidney, analytical methodologyand drug metabolism/pharmacokinetics. He

Chapman, et al., Nano Today (2013),

eceived his BS. degree in biochemistry from the University ofochester and PhD in toxicology from the University of Connecti-ut at Storrs. Dr. Stern is a Diplomate of the American Board ofoxicology.

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Dr. Wang is a physician-scientist at theLineberger Comprehensive Cancer Center,University of North Carolina-Chapel Hill. Hisresearch is focused on the clinical transla-tion of nanoparticle therapeutics to cancertreatment. Clinically, he specializes in thetreatment of gastrointestinal and genitouri-nary cancers.

John B. Weaver is a Professor of Radiology inthe Geisel School of Medicine at DartmouthCollege with adjunct appointments in theThayer School of Engineering and the Depart-ment of Physics at Dartmouth College. Hereceived his BS from the University of Arizonain 1977, his PhD in Biophysics from the Univer-sity of Virginia in 1983 and worked for SiemensMedical Systems until 1985 when he joined

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the Dartmouth faculty. His early research wasin fast MR imaging and image processing using

wavelet methods. His current research is in sensing and imagingmagnetic nanoparticles and in MR elastography.

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Gayle Woloschak is Professor of RadiationOncology, Radiology, and Cell and MolecularBiology, and Associate Director of the Cen-ters of Cancer Nanotechnology Excellence inthe Robert H. Lurie Comprehensive CancerCenter, Northwestern University. Prior to 2001she and her research group were at ArgonneNational Laboratory. Gayle received her BS.in Biological Sciences from Youngstown StateUniversity and a PhD in Medical Sciences fromthe Medical College of Ohio. She did her post-

octoral training at the Mayo Clinic, where she was later became anssistant Professor there. Her scientific interests are predominantly

n the areas of Radiobiology and Nanotechnology studies, and sheas authored over 180 scientific papers.

Dr. Lily Yang is Professor and Nancy PanozChair of Surgery in Cancer Research atEmory University School of Medicine. Dr. Yangreceived her medical training in China atWest China University of Medical Sciencesand then in the Chinese Academy of Preven-tive Medicine. She received her PhD degreein Molecular and Cellular Biology Program atBrown University. Dr. Yang’s research projectsfocus on the development of novel cancer

Chapman, et al., Nano Today (2013),

nanotechnologies and imaging methods toddress the major challenges in clinical oncology of early can-er detection, targeted drug delivery, assessment of therapeuticesponse using non-invasive imaging, and image-guided surgery.