Insights from imaging in bioinorganic chemistry

509 Pages·2016·56.924 MB·English

by  Eldik, Rudi van, Hubbard, Colin D

ADVISORY BOARD
L. H. Gade D. Darensbourg
UniversitätHeidelberg TexasA&MUniversity
Germany CollegeStation,Texas,USA
M. L. H. Green H. B. Gray
UniversityofOxford CaliforniaInstituteofTechnology
Oxford,UnitedKingdom Pasadena,California,USA
A. E. Merbach P. A. Lay
LaboratoiredeChimieetBioanorganiqueEFPL, UniversityofSydney
Lausanne,Switzerland Sydney,Australia
P. J. Sadler J. Reedijk
UniversityofWarwick LeidenUniversity
Warwick,England Leiden,TheNetherlands
K. Wieghardt Y. Sasaki
Max-Planck-Institut HokkaidoUniversity
Mülheim,Germany Sapporo,Japan
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CONTRIBUTORS
EricaAndreozzi
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
StephenJ.Archibald
DepartmentofChemistry,PositronEmissionTomographyResearchCentre,Universityof
Hull,Hull,UnitedKingdom
JuliaBagunya-Torres
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
PhilipJ.Blower
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
EwenBodio
InstitutdeChimieMol(cid:1)eculairedel’Universit(cid:1)edeBourgogne,UMR6302,CNRS,Univ.
BourgogneFranche-Comt(cid:1)e,Dijon,France
C(cid:1)eliaS.Bonnet
CentredeBiophysiqueMol(cid:1)eculaire,CNRS,UPR4301,Universit(cid:1)ed’Orl(cid:1)eans,Orl(cid:1)eans,
France
RossW.Boyle
DepartmentofChemistry,UniversityofHull,Hull,UnitedKingdom
FrancescaBryden
DepartmentofChemistry,UniversityofHull,Hull,UnitedKingdom
BenjaminP.Burke
DepartmentofChemistry,PositronEmissionTomographyResearchCentre,Universityof
Hull,Hull,UnitedKingdom
DavidG.Calatayud
ChemistryDepartment,UniversityofBath,Bath,UnitedKingdom
FranckDenat
InstitutdeChimieMol(cid:1)eculairedel’Universit(cid:1)edeBourgogne,UMR6302,CNRS,Univ.
BourgogneFranche-Comt(cid:1)e,Dijon,France
PaulS.Donnelly
SchoolofChemistryandBio21MolecularScienceandBiotechnologyInstitute,
TheUniversityofMelbourne,Parkville,Victoria,Australia
GilbertFruhwirth
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
ix
x Contributors
DipGill
DepartmentofChemistryandCentreforAdvancedStudiesinChemistry,PanjabUniversity,
Chandigarh,India
ChristineGoze
InstitutdeChimieMol(cid:1)eculairedel’Universit(cid:1)edeBourgogne,UMR6302,CNRS,Univ.
BourgogneFranche-Comt(cid:1)e,Dijon,France
CinziaImberti
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
PierreLeGendre
InstitutdeChimieMol(cid:1)eculairedel’Universit(cid:1)edeBourgogne,UMR6302,CNRS,Univ.
BourgogneFranche-Comt(cid:1)e,Dijon,France
KennethKam-WingLo
DepartmentofBiologyandChemistry,CityUniversityofHongKong,HongKong,
PRChina
MichelleT.Ma
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
HelmutR.Maecke
DepartmentofNuclearMedicine,UniversityHospitalFreiburg,Freiburg,Germany
BoyangMao
ChemistryDepartment,UniversityofBath,Bath,UnitedKingdom
LeventeK.Meszaros
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
VincenzoMirabello
ChemistryDepartment,UniversityofBath,Bath,UnitedKingdom
GregoryE.D.Mullen
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
SubhaniM.Okarvi
CyclotronandRadiopharmaceuticalsDepartment,KingFaisalSpecialistHospitaland
ResearchCentre,Riyadh,SaudiArabia
SofiaI.Pascu
ChemistryDepartment,UniversityofBath,Bath,UnitedKingdom
BrettM.Paterson
SchoolofChemistryandBio21MolecularScienceandBiotechnologyInstitute,
TheUniversityofMelbourne,Parkville,Victoria,Australia
VivekPathania
DAVCollege,Sector10,Chandigarh,India
Contributors xi
JohannaSeemann
DepartmentofChemistry,PositronEmissionTomographyResearchCentre,Universityof
Hull,Hull,UnitedKingdom
RichardSouthworth
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
RafaelTorresMartindeRosales
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
(cid:1)
EvaTo´th
CentredeBiophysiqueMol(cid:1)eculaire,CNRS,UPR4301,Universit(cid:1)ed’Orl(cid:1)eans,Orl(cid:1)eans,
France
JamesA.Tyson
ChemistryDepartment,UniversityofBath,Bath,UnitedKingdom
JenniferD.Young
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’s
CollegeLondon,London,UnitedKingdom
PREFACE
Volume 68 of Advances in Inorganic Chemistry has a predominant theme of
metal ions in medical imaging. Colin D. Hubbard of the University of
NewHampshireisservingascoeditor.Thereisaconsiderableamountoftra-
ditional inorganicchemistry in thesense ofthe rationale forchoiceofmetal
ionsinparticularcontexts,andtherelevantcoordinationchemistry.Inmany
contributions,thedesignofsuitablechelatingligandsfortheproposedappli-
cationofthemetalcomplexisdebated.Thisleadstocreativeideasoforganic
synthesisthatwouldleadtocomplexesofthedesiredproperties.Beyondwhat
maybethoughtofastraditionalinorganicchemistry,thereispresentationofa
widearrayofmethodsandtechniquesthatareusedinthebiomedicalscience
fieldtoexploitthepropertiesofthespeciesproducedforimaging.Complexes
for magnetic resonance, luminescent metal complexes, metalloporphyrins,
and radiopharmaceutical complexes are among the species highlighted in
these contributions from experts. The scientific content ranges from in vitro
coordinationchemistrytoinvivotreatmentinclinicalpractice,arangeman-
ifest in the titles of the different contributions. It is emphasized that the
research advances described, beside their intrinsic authoritative value, are of
inestimable value in the areas of diagnosis and therapy within biomedical
science and public health services.
InChapter1,PhilipBlowerandcollaboratorspresentanexpertoverview
andassessmentofthecurrentstatusofmetalchemistryinmedicalimaging;it
includesaninsightintothechallengesandpathstosuccessesandpossibilitiesfor
futureprogress.ThisisfollowedbyacontributionfromE(cid:1)vaTo´thandC(cid:1)elia
Bonnet (Chapter 2) that describes recent progress in the development of
molecular magnetic imaging probes based upon lanthanide complexes, a
chapter illustrating the subtleties of preparing Ln3+ complexes with suitable
chelating molecules that provide optimal results. Kenneth Kam-Wing Lo,
inChapter3,presentsafascinatingaccountofhisrecentdevelopmentofboth
iridium(III)andrhenium(I)complexesthatexhibitluminescentpropertiesthat
maybeexploitedasbiomolecularprobesandimagingreagents.InChapter4,
Francesca Bryden and Ross Boyledemonstratetheir successes in usingmet-
alloporphyrins for medical imaging applications. A contribution from Brett
PatersonandPaulDonnelly,Chapter5,drawsinspirationfromtheliterature
of organic chemistry in creating macrocyclic bifunctional chelators; they
indicate their conjugation strategies for the development of copper-64
xiii
xiv Preface
radiopharmaceuticals. Christine Goze and colleagues have described their
approachtothedevelopmentofanticanceragents,basedonmetalcomplexes,
whoseprogresscanbetracked,inChapter6.StephenArchibaldandcollab-
oratorshavedescribedinChapter7thedesignfeaturestheyemployinprepar-
ingchelatingmoleculesformetalcomplexesinimagingapplicationsinvolving
radiopharmaceuticals, protein targeting, and conjugation aspects. Subhani
Okarvi and HelmutMaecke takereaders ona journeyfrom thepreparation
of radiometallo-labeled peptides to their use in tumor diagnosis in models
and in targeted radionuclide therapy in clinical practice, within Chapter 8.
Onthetopicofimaging,SofiaPascuandcolleaguesreview,inChapter9,very
recentactivitiesinthefieldoflabelingofgraphene,grapheneoxide,andtheir
congenersforimagingandbiosensingapplicationsthatareofrelevancetocan-
certheranostics.InVolume58ofAdvancesinInorganicChemistrypublishedin
2006,severalreviewsweredevotedtotheroleofcopper-dioxygencomplexes
in biomimetic substrate oxidation reactions. As a complementary contribu-
tion, a presentation of Cu(I) chemistry in nonaqueous solvents, principally
nitriles,byDipGillandVivekPathaniawasreceived,edited,andisincluded
inthisvolume(Chapter10).Incontrasttoaqueousmedia,Cu(I)isstabilized
bythesesolvents.
The editors are most appreciative of the efforts of the authors and their
colleagues who have provided informative, instructive, and authoritative
contributions for this thematic volume. It will be a valuable resource for
both newcomers and established investigators in the biomedical science
community, and particularly, for those who are directly involved in the
overallfieldofimaging,aswellasotherbioinorganicchemistryinvestigators.
We invite readers in other fields of chemistry to acquaint themselves with
the fascinating and intriguing challenges awaiting further developments in
various forms of imaging, in the years to come.
RUDI VAN ELDIK
Editor of Advances in Inorganic Chemistry
Emeritus Professor of Inorganic Chemistry,
Professor of Inorganic Chemistry, Jagiellonian University,
Krakow, Poland
COLIN D. HUBBARD
Coeditor of this volume
Emeritus Professor of Chemistry,
University of New Hampshire, USA
December 2015
CHAPTER ONE
Opportunities and Challenges
for Metal Chemistry in
Molecular Imaging: From Gamma
Camera Imaging to PET and
Multimodality Imaging
Richard Southworth, Rafael Torres Martin de Rosales,
Levente K. Meszaros, Michelle T. Ma, Gregory E.D. Mullen,
Gilbert Fruhwirth, Jennifer D. Young, Cinzia Imberti,
Julia Bagunya-Torres, Erica Andreozzi, Philip J. Blower1
DivisionofImagingSciencesandBiomedicalEngineering,St.ThomasHospital,King’sCollegeLondon,
London,UnitedKingdom
1Correspondingauthor:e-mailaddress:[email protected]
Contents
1. Introduction 2
2. Technetium-99m:SmallComplexes 4
2.1 FromSerendipitytoDesign 4
2.2 Tc(I)tricarbonyl 5
2.3 Tc(V)Complexes 6
2.4 Bioconjugates:ANewChallenge 8
2.5 BioconjugationwithHynic 8
2.6 BioconjugationwithOtherBifunctionalChelators 10
2.7 Bioconjugationwiththe“TricarbonylCore”Tc(CO) + 10
3
2.8 BioconjugationbyDirectLabelingViaCysteine 12
2.9 RheniumAnalogs 13
2.10 Summary:ChallengesinTc-99mChemistry 13
3. TheTransitionTowardPET 14
3.1 TheNeedforMetallicPositronEmitters 14
3.2 Gallium-68:“TheNewTechnetium-99m” 14
3.3 Zirconium-89:“TheNewIndium-111”—ImmunoPETandCellTracking 17
4. Copper:ExploitingRedoxChemistry 19
4.1 CopperIsotopesandBioconjugates 19
4.2 BioreductiveTrapping—ImagingBloodFlowandHypoxia 21
4.3 CellTrackingwithCopper 28
4.4 CopperTraffickingPathwaysinHealthandDisease 29
5. InorganicElementsasBindingSitesfor18F-Fluoride 31
AdvancesinInorganicChemistry,Volume68 #2016ElsevierInc. 1
ISSN0898-8838 Allrightsreserved.
http://dx.doi.org/10.1016/bs.adioch.2015.09.001
2 RichardSouthworthetal.
6. MultimodalityImagingandNanoparticulateContrastAgents 32
7. SummaryandConclusion 35
Acknowledgments 36
References 36
Abstract
Thedevelopmentofmedicalimagingisahighlymultidisciplinaryendeavorrequiring
the close cooperation of clinicians, physicists, engineers, biologists, and chemists to
identify capabilities, conceive challenges and solutions and apply them in the clinic.
Thechemistry described in this chapter illustrates howsynergistic advances in these
areasdrivethetechnologyanditsapplicationsforward,witheachdisciplineproducing
innovations that in turn drive innovations in the others. The main thread running
through the chapter is the shift from single photon radionuclide imaging toward
PET,andinturntheemergingshiftfromPET/CTtowardPET/MRIandfurther,combina-
tionofthesewithopticalimaging.Chemistrytosupportthesetransitionsisexemplified
bybuildingonasummaryofthestatusquo,andrecentdevelopments,intechnetium-
99mchemistryforSPECTimaging,followedbyareportofrecentdevelopmentstosup-
portclinicalapplicationofshort-lived(Ga-68)andlong-lived(Zr-89)positron-emitting
isotopes, copper isotopes for PET imaging, and combined modality imaging agents
basedonradiolabeledironoxide-basednanoparticles.
1. INTRODUCTION
Nuclear medicine is a primarily diagnostic medical imaging specialty
in which tracer molecules targeted toward specific molecular processes are
labeled with radioisotopes, and used to spatially and temporally map phys-
iologicalandmolecularprocessesinthebody,todiagnosediseaseandmake
patient managementdecisions (1,2).Theuseofunsealedartificial radionu-
clidesformedicalpurposesinhumanscanbetracedbacktotheexperimental
use of 24Na-sodium chloride by Hamilton and Stone in 1936 (3), closely
followed by administration of 32P-phosphate by John Lawrence in
1937–1939 (3) to patients with hematological diseases and 131I-iodide by
Hamilton to patients with thyroid disease. Later 131I-iodide became
established for treating thyroid disease. However, the use of radioisotopes
for diagnostic medical imaging did not become routine in hospitals until
the1970s,followingtheintroductionofthefirstcommercialgammacamera
in 1968 (4) (and later, its evolution into single photon emission computed
tomography (SPECT)). Equally important in the rise of nuclear medicine
was the 99mTc generator, first used for medical purposes in 1961 (4) and
OpportunitiesandChallengesforMetalChemistryinMolecularImaging 3
firmlyestablishedinroutinepracticebythe1970s.Thissimpledevicesolved
theproblem of world-widedistribution ofshort half-life radionuclidesand
enabled hospitals, for the first time, to have daily access to a radionuclide
withexcellentimagingproperties:agammaemissionspectrumwithasingle
photopeak at 140KeV, offering a good balance between low attenuation
and efficient detection outside the body, low radiation dose to patients
becauseofitslackofparticulateemissionsandshorthalf-life(6h),andver-
satilechemistry.Bymeansofthegenerator,99Mo,anuclearreactor-derived
beta-emitting radionuclide with a half-life of 60h, could be transported to
hospitalsaroundtheworldintheformofmolybdate(MoO 2(cid:1))ionsbound
4
toasolidphase(alumina).Asthe99Modecaysto99mTc,thedaughterprod-
uctpertechnetate(99mTcO (cid:1))canbeelutedfromthesolidphasewithsterile
4
physiological saline and converted into a variety of different tracers for a
rangeofdiagnosticapplications.Therangeof99mTc-radiolabeledchemical
entitiesthatquicklybecameaccessiblefollowingtheavailabilityofthegen-
erator, combined with the ease of their synthesis on the hospital site by
means of simple kits (vials containing the chemical ingredients needed to
convertthe99mTcfromthe“raw”pertechnetateintotherequiredchemical
form)firmlyestablished99mTcasthemostwidelyusedradionuclideinmed-
icine, and brought a focus on metallic radionuclides as a field in which
metallochemistry could find valuable biomedical applications. Early tracers
rangedfromsimplelipophiliccomplexesforhepatobiliaryimagingtosimple
anionic hydrophilic complexes for renal function imaging, and bis-
phosphonate complexes for skeletal imaging.
Although the conceptof positronemission tomography (PET) evolved
aroundthesametimeasgammacameraimaging,itdidnotdevelopfroma
research tool into a widely used clinical diagnostic tool until the 1990s. Its
expansionwasprimarilydrivenbytheintroductionofthefirstPETtracerof
wide utility in many diseases, the glucose analog 18F-fluorodeoxyglucose,
usedprimarilyforidentifyingandstagingcancer.WhilePEThastheadvan-
tageofbetterresolutionandquantificationthangammacameraandSPECT
imaging,theshorthalf-lifeofmanyofitstracers(e.g.,only110minfor18F)
demandedsignificantinvestmentininfrastructure,requiringcyclotronfacil-
itiestobeinstalledatlocationswithin2–4htravelingdistanceofPETscan-
ners. The availability of the new imaging modality spawned interest in
developing a much wider variety of PET tracers, to enhance its versatility.
This created not only applications for organic chemists to develop tracers
based on small molecule metabolites and receptor ligands labeled with the
positronemitters18Fand11C,butalsoopportunitiesforinorganicchemists