Contrast agents for MRI : experimental methods

612 Pages·2018·17.39 MB·English

by  Valérie C Pierre

Contrast Agents for MRI
Experimental Methods
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New Developments in NMR
Editor-in-Chief:
William S. Price, Western Sydney University, Australia
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6-F Series Editors:
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1 Sharon Ashbrook, University of St Andrews, UK
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0 Bruce Balcom, University of New Brunswick, Canada
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78 Istv´an Furo´, Industrial NMR Centre at KTH, Sweden
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9/ Maili Liu, Chinese Academy of Sciences, Wuhan, China
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13: Contrast Agents for MRI: Experimental Methods
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Contrast Agents for MRI
Experimental Methods
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01 Edited by
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sc. ISSN:2044-253X
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1 Preface
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oi: The field of contrast agents for magnetic resonance imaging (MRI) has
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g | progressed by leaps and bounds over the last few decades, from metal
or complexestoresponsiveandtargetedprobesthatenablemulticolorimaging
c.
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s.r with remarkable resolution and sensitivity. Along the way, our understand-
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u ing of the richness of the coordination chemistry of lanthanide and transi-
p
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htt chemical and physical parameters to achieve new types of contrast. The
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er now widely appreciated.
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e Asthisfieldprogressesquickly,thebreadthofthetechniquesusedinthe
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No synthesis and characterization of contrast agents can seem overwhelming.
. n 08 This book is not a classical review of the literature; many excellent reviews
o andbooksexistthatservethatpurpose.Rather,ourintentionisforthisbook
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he to serve as a benchtop companion for chemists, physicists, and biologists.
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bli Throughout this book, different techniques that are used in the field of
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contrast agents for MRI are described. The strengths and limitations of the
techniques are discussed together with a summary of the information that
those techniques can and cannot provide and descriptions of how to inter-
pret data. This book is intended not only for those working on the design,
synthesis, and evaluation of contrast agents, but also on their medical and
biological applications. It is intended for students, postdoctoral scholars
and researchers working in the lab, and also for those writing manuscripts
and grant applications. Throughout its chapters, this book provides infor-
mation that is intended to help in the design of contrast agents to fill spe-
cific needs and guides readers through synthesis, characterization,
evaluation, and determination of the chemical, physical, and biological
properties of new contrast agents.
NewDevelopmentsinNMRNo.13
ContrastAgentsforMRI:ExperimentalMethods
EditedbyVal´erieC.PierreandMatthewJ.Allen
rTheRoyalSocietyofChemistry2018
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
v
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vi Preface
Thefirstchapterofthisbookdiscussesthesynthesisandcharacterization
of metal-based contrast agents. Ligand choice affects not only the contrast-
enhancing ability of an agent but also its thermodynamic stability and
kinetic inertness, which are paramount to the safety profiles of probes.
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F detail the techniques relevant to specific classes of contrast agents:
46- GdIII-based contrast agents (Chapter 2), chemical exchange saturation
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1 transfer agents (Chapter 3), nanoparticle-based contrast agents (Chapter 4),
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8 transition-metal based T -shortening contrast agents (Chapter 5), and
7 1
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8 fluorine probes (Chapter 6). In each chapter, the principles underlying that
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9/ classofcontrastagentandthephysicalexperimentsuniquelysuitedtotheir
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10 studiesaredescribed.Thebookfinisheswithachapterfocusedonbiological
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1 andpharmacologicalexperimentsthatarekeytoevaluatingthepotentialof
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d contrast agents for use in vivo.
org | Thisbookwouldnothavebeenpossiblewithoutsubstantialcontributions
sc. from the world-renowned experts who authored the chapters. To each of
bs.r them, we offer our most sincere and largest possible thank you! We are
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p://p especially indebted to Susan A. White, who downloaded, reviewed, and
htt edited every single reference of this book. We also gratefully acknowledge
on DrSylviePailloux,whocontributedtotheeditingofafewsubchapters.Both
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1 of us thank our research groups for their patience as we spent time editing
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mb their unwavering support throughout this journey.
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v Tothereader,wehopethisbookwillguideyouthroughyourownjourney
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1 Contents
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1 Chapter 1 General Synthetic and Physical Methods 1
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oi: QuyenN.Do,JamesS.Ratnakar,Zolta´nKova´cs,GyulaTircso´,
g | d Ferenc Krisztia´n Ka´lma´n, Zsolt Baranyai, Erno+ Bru¨cher and
or Imre To´th
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. n 0 1.2.2 Characterization of Metal Complexes 34
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Metal–Ligand Interactions 41
1.3.3 Equilibrium Models 46
1.3.4 PhysicochemicalMethodsforCharacterizing
Metal–Ligand Interactions 51
1.3.5 Stabilities of Gadolinium Complexes:
Selected Examples 69
1.3.6 Acknowledgements 74
1.4 Lability of Metal Complexes 75
1.4.1 Introduction 75
1.4.2 Dissociation Kinetics of Metal Chelates 76
NewDevelopmentsinNMRNo.13
ContrastAgentsforMRI:ExperimentalMethods
EditedbyVal´erieC.PierreandMatthewJ.Allen
rTheRoyalSocietyofChemistry2018
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
vii
View Online
viii Contents
1.4.3 Methods for Kinetic Studies 81
1.4.4 Decomplexation Reactions near
Physiological Conditions 82
1.4.5 Effect of Ligand Structure on the Inertness
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oi:1 Rosa Pujales-Paradela, Mart´ın Regueiro-Figueroa,
g | d David Esteban-Go´mez, Carlos Platas-Iglesias and
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2.3.2 Theory and Interpretation of NMRD
Profiles 136
2.4 Measuring Water Coordination Numbers (q) 139
2.4.1 Hydration: Inner- Versus Outer-Sphere
Water Ligands 139
2.4.2 Oxygen-17 NMR Spectroscopy 139
2.4.3 Luminescence Spectroscopy 142
2.4.4 Electron Nuclear Double Resonance 149
2.4.5 Single Crystal X-ray Diffraction 151
2.4.6 Extended X-ray Absorbance Fine Structure
Spectroscopy 151
2.5 Measuring Rotational Correlation Times (t ) 153
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2.5.1 Fit of NMRD Profiles 154
2.5.2 Debye–Stokes Equation 156
2.5.3 Oxygen-17 1/T NMR Spectroscopy 156
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Contents ix
2.5.5 Carbon-13-NMR Spectroscopy 158
2.5.6 Hydrogen-NMR Longitudinal Relaxation
Rates (Curie Mechanism) 161
2.6 Measuring Water Residence Times (t ) 164
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org | 2.7.2 Mineralization Monitored by NMR
sc. Relaxometry 175
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ber 2.8.1 Determination of the Binding Parameters:
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2.9.2 Semi-empirical Calculations 198
2.9.3 Density Functional Theory and Ab Initio
Methods 198
2.9.4 Basis Sets and Relativistic Effects 203
2.9.5 Solvent Effects 205
2.9.6 Practical Aspects and Selected Examples 207
2.9.7 Software 214
2.9.8 Acknowledgements 214
2.10 Acquiring Phantom Images 215
2.10.1 Image Formation in MRI 215
2.10.2 MRI Pulse Sequences 222
2.10.3 Effect of T and T on Image Contrast 224
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2.10.4 MeasurementofT andT TimeConstants
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by MRI 225
2.10.5 Field-strength Dependencies 228
References 229
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x Contents
Chapter 3 Chemical Exchange Saturation Transfer (CEST) Contrast
Agents 243
Giuseppe Ferrauto, Silvio Aime, Michael T. McMahon,
Janet R. Morrow, Eric M. Snyder, Alex Li and Robert Bartha
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g | PARACEST Agents 257
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Pu Complexes That Also Apply to CEST Agents 269
3.4 Determining Proton Exchange Rates (k ) 274
ex
3.4.1 Introduction to Proton Exchange 274
3.4.2 Linewidth Measurement for Assessing
Exchange Rate 274
3.4.3 WEX Experiments for Assessing
Exchange Rate 275
3.4.4 QUEST and QUESP Experiments for
Assessing Exchange Rate 275
3.4.5 Acknowledgements 279
3.5 Preparation and Characterization of Paramagnetic
Micelles and Liposomes 280
3.5.1 Routes to Enhance the Sensitivity of CEST
Agents 280
3.5.2 Preparation and Characterization of
Paramagnetic CEST Micelles 281