The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging
2. Auflage April 2013
512 Seiten, Hardcover
Wiley & Sons Ltd
ISBN:
978-1-119-99176-2
John Wiley & Sons
Kurzbeschreibung
Magnetic Resonance Imaging (MRI) is one of the most important tools in clinical diagnostics and biomedical research. This completely revised and extended second edition is presented in color and includes new chapters on targeted, responsive, PARACEST and nanoparticle MRI contrast agents. It covers the basic chemistries, MR physics and most important techniques used by chemists in the characterization of MRI agents from every angle, from synthesis to safety considerations. Essential reading for professionals involved in the development and application of contrast agents in MRI.
Magnetic Resonance Imaging (MRI) is one of the most important tools in clinical diagnostics and biomedical research. This completely revised and extended second edition is presented in color and includes new chapters on targeted, responsive, PARACEST and nanoparticle MRI contrast agents. It covers the basic chemistries, MR physics and most important techniques used by chemists in the characterization of MRI agents from every angle, from synthesis to safety considerations. Essential reading for professionals involved in the development and application of contrast agents in MRI.
List of Contributors xiii
Preface xv
1 General Principles of MRI 1
Bich-Thuy Doan, Sandra Meme, and Jean-Claude Beloeil
1.1 Introduction 1
1.2 Theoretical basis of NMR 1
1.3 Principles of magnetic resonance imaging 5
1.4 MRI pulse sequences 11
1.5 Basic image contrast: Tissue characterization without injection of contrast agents (main contrast of an MRI sequence: Proton density (P), T1 and T2, T* 2) 16
1.6 Main contrast agents 18
1.7 Examples of specialized MRI pulse sequences for angiography (MRA) 21
References 23
2 Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism 25
E´va To´th, Lothar Helm, and Andre´ Merbach
2.1 Introduction 25
2.2 Inner-sphere proton relaxivity 28
2.3 Second- and outer-sphere relaxation 64
2.4 Relaxivity and NMRD profiles 66
2.5 Design of high relaxivity agents: Summary 75
References 76
3 Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes 83
Jan Kotek, Vojt¢§ech Kub´(c)¥¢§cek, Petr Hermann, and Ivan Luke¢§s
3.1 Introduction - general requirements for the ligands and complexes 83
3.2 Contrast agents employing linear polyamine scaffold 84
3.3 Contrast agents employing cyclen scaffold 103
3.4 Other types of ligands 123
3.5 Bifunctional ligands and their conjugations 134
3.6 Synthesis and characterization of the Ln(III) complexes 138
List of Abbreviations 144
References 146
4 Stability and Toxicity of Contrast Agents 157
Ern~o Br¨ucher, Gyula Tircs´o, Zsolt Baranyai, Zolt´an Kov´acs, and A. Dean Sherry
4.1 Introduction 157
4.2 Equilibrium calculations 158
4.3 Stability of metal-ligand complexes 160
4.4 Kinetics of M(L) complex formation 184
4.5 Dissociation of M(L) complexes 186
4.6 Biodistribution and in vivo toxicity of Gd3+-based MRI contrast agents 193
4.7 Concluding remarks 201
Acknowledgements 201
References 201
5 Structure, Dynamics, and Computational Studies of Lanthanide-Based Contrast Agents 209
Joop A. Peters, Kristina Djanashvili, Carlos F.G.C. Geraldes, and Carlos Platas-Iglesias
5.1 Introduction 209
5.2 Computational methods 210
5.3 Lanthanide-induced NMR shifts 213
5.4 Lanthanide-induced relaxation rate enhancements 219
5.5 Anisotropic hyperfine interactions on the first coordination sphere water molecules 221
5.6 Evaluation of geometries by fitting NMR parameters 222
5.7 Two-dimensional NMR 224
5.8 139La and 89Y NMR 224
5.9 Water hydration numbers 225
5.10 Chirality of lanthanide complexes of polyaminocarboxylates 227
5.11 Complexes of non-macrocyclic polyaminocarboxylates 227
5.12 Complexes of macrocyclic ligands 244
5.13 Fullerenes 265
References 267
6 Electronic Spin Relaxation and Outer-Sphere Dynamics of Gadolinium-Based Contrast Agents 277
Pascal H. Fries and Elie Belorizky
6.1 Introduction 277
6.2 Theory of electronic spin relaxation of Gd3+ ions 279
6.3 Outer-sphere dynamics 289
6.4 Relaxivity quenching by the electronic spin relaxation 295
6.5 Various experimental approaches of the electronic spin relaxation 301
6.6 Conclusion and perspectives 306
6.A Appendix: Similar evolutions of the macroscopic magnetization of the electronic spin and of its correlation functions 307
References 308
7 Targeted MRI Contrast Agents 311
Peter Caravan and Zhaoda Zhang
7.1 Introduction 311
7.2 Serum albumin 313
7.3 Fibrin 319
7.4 Type I collagen 325
7.5 Elastin 326
7.6 Sialic acid 327
7.7 alphaVß3 integrin 328
7.8 Folate receptor 329
7.9 Matrix metalloproteinases (MMP) 330
7.10 E-selectin 331
7.11 Fibrin-fibronectin complex 332
7.12 Alanine aminopeptidase (CD13) 332
7.13 Carbonic anhydrase 333
7.14 Interleukin 6 receptor 334
7.15 Estrogen and progesterone receptors 335
7.16 Contrast agents based on natural products 336
7.17 Messenger RNA (mRNA) 337
7.18 Myelin 338
7.19 DNA 338
7.20 Conclusions 340
References 340
8 Responsive Probes 343
Ce´lia S. Bonnet, Lorenzo Tei, Mauro Botta, and E´va To´th
8.1 Introduction 343
8.2 Probes responsive to physiological parameters 344
8.3 Conclusions 381
References 382
9 Paramagnetic CEST MRI Contrast Agents 387
Enzo Terreno, Daniela Delli Castelli, and Silvio Aime
9.1 Introduction 387
9.2 Theoretical and practical considerations on CEST response 388
9.3 Diamagnetic versus paramagnetic CEST agents 400
9.4 Paramagnetic CEST agents 401
9.5 Other exchange-mediated contrast modes accessible for paramagnetic CEST agents 419
9.6 Concluding remarks 421
References 421
10 Superparamagnetic Iron Oxide Nanoparticles for MRI 427
Sophie Laurent, Luce Vander Elst, and Robert N. Muller
10.1 Introduction 427
10.2 Synthesis of iron oxide nanoparticles 428
10.3 Stabilization 431
10.4 Methods of vectorization for molecular imaging 432
10.5 Characterization 436
10.6 Applications 440
10.7 Conclusions 444
Acknowledgements 444
References 444
11 Gd-Containing Nanoparticles as MRI Contrast Agents 449
Klaas Nicolay, Gustav Strijkers, and Holger Gr¨ull
11.1 Introduction 449
11.2 Length scales and excretion pathways 452
11.3 Preparation of Gd-containing nanoparticles 454
11.4 Methods for nanoparticle characterization 460
11.5 In vitro applications 468
11.6 In vivo applications 475
11.7 Conclusions and future perspectives 481
Acknowledgements 483
References 483
Index 489
Preface xv
1 General Principles of MRI 1
Bich-Thuy Doan, Sandra Meme, and Jean-Claude Beloeil
1.1 Introduction 1
1.2 Theoretical basis of NMR 1
1.3 Principles of magnetic resonance imaging 5
1.4 MRI pulse sequences 11
1.5 Basic image contrast: Tissue characterization without injection of contrast agents (main contrast of an MRI sequence: Proton density (P), T1 and T2, T* 2) 16
1.6 Main contrast agents 18
1.7 Examples of specialized MRI pulse sequences for angiography (MRA) 21
References 23
2 Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism 25
E´va To´th, Lothar Helm, and Andre´ Merbach
2.1 Introduction 25
2.2 Inner-sphere proton relaxivity 28
2.3 Second- and outer-sphere relaxation 64
2.4 Relaxivity and NMRD profiles 66
2.5 Design of high relaxivity agents: Summary 75
References 76
3 Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes 83
Jan Kotek, Vojt¢§ech Kub´(c)¥¢§cek, Petr Hermann, and Ivan Luke¢§s
3.1 Introduction - general requirements for the ligands and complexes 83
3.2 Contrast agents employing linear polyamine scaffold 84
3.3 Contrast agents employing cyclen scaffold 103
3.4 Other types of ligands 123
3.5 Bifunctional ligands and their conjugations 134
3.6 Synthesis and characterization of the Ln(III) complexes 138
List of Abbreviations 144
References 146
4 Stability and Toxicity of Contrast Agents 157
Ern~o Br¨ucher, Gyula Tircs´o, Zsolt Baranyai, Zolt´an Kov´acs, and A. Dean Sherry
4.1 Introduction 157
4.2 Equilibrium calculations 158
4.3 Stability of metal-ligand complexes 160
4.4 Kinetics of M(L) complex formation 184
4.5 Dissociation of M(L) complexes 186
4.6 Biodistribution and in vivo toxicity of Gd3+-based MRI contrast agents 193
4.7 Concluding remarks 201
Acknowledgements 201
References 201
5 Structure, Dynamics, and Computational Studies of Lanthanide-Based Contrast Agents 209
Joop A. Peters, Kristina Djanashvili, Carlos F.G.C. Geraldes, and Carlos Platas-Iglesias
5.1 Introduction 209
5.2 Computational methods 210
5.3 Lanthanide-induced NMR shifts 213
5.4 Lanthanide-induced relaxation rate enhancements 219
5.5 Anisotropic hyperfine interactions on the first coordination sphere water molecules 221
5.6 Evaluation of geometries by fitting NMR parameters 222
5.7 Two-dimensional NMR 224
5.8 139La and 89Y NMR 224
5.9 Water hydration numbers 225
5.10 Chirality of lanthanide complexes of polyaminocarboxylates 227
5.11 Complexes of non-macrocyclic polyaminocarboxylates 227
5.12 Complexes of macrocyclic ligands 244
5.13 Fullerenes 265
References 267
6 Electronic Spin Relaxation and Outer-Sphere Dynamics of Gadolinium-Based Contrast Agents 277
Pascal H. Fries and Elie Belorizky
6.1 Introduction 277
6.2 Theory of electronic spin relaxation of Gd3+ ions 279
6.3 Outer-sphere dynamics 289
6.4 Relaxivity quenching by the electronic spin relaxation 295
6.5 Various experimental approaches of the electronic spin relaxation 301
6.6 Conclusion and perspectives 306
6.A Appendix: Similar evolutions of the macroscopic magnetization of the electronic spin and of its correlation functions 307
References 308
7 Targeted MRI Contrast Agents 311
Peter Caravan and Zhaoda Zhang
7.1 Introduction 311
7.2 Serum albumin 313
7.3 Fibrin 319
7.4 Type I collagen 325
7.5 Elastin 326
7.6 Sialic acid 327
7.7 alphaVß3 integrin 328
7.8 Folate receptor 329
7.9 Matrix metalloproteinases (MMP) 330
7.10 E-selectin 331
7.11 Fibrin-fibronectin complex 332
7.12 Alanine aminopeptidase (CD13) 332
7.13 Carbonic anhydrase 333
7.14 Interleukin 6 receptor 334
7.15 Estrogen and progesterone receptors 335
7.16 Contrast agents based on natural products 336
7.17 Messenger RNA (mRNA) 337
7.18 Myelin 338
7.19 DNA 338
7.20 Conclusions 340
References 340
8 Responsive Probes 343
Ce´lia S. Bonnet, Lorenzo Tei, Mauro Botta, and E´va To´th
8.1 Introduction 343
8.2 Probes responsive to physiological parameters 344
8.3 Conclusions 381
References 382
9 Paramagnetic CEST MRI Contrast Agents 387
Enzo Terreno, Daniela Delli Castelli, and Silvio Aime
9.1 Introduction 387
9.2 Theoretical and practical considerations on CEST response 388
9.3 Diamagnetic versus paramagnetic CEST agents 400
9.4 Paramagnetic CEST agents 401
9.5 Other exchange-mediated contrast modes accessible for paramagnetic CEST agents 419
9.6 Concluding remarks 421
References 421
10 Superparamagnetic Iron Oxide Nanoparticles for MRI 427
Sophie Laurent, Luce Vander Elst, and Robert N. Muller
10.1 Introduction 427
10.2 Synthesis of iron oxide nanoparticles 428
10.3 Stabilization 431
10.4 Methods of vectorization for molecular imaging 432
10.5 Characterization 436
10.6 Applications 440
10.7 Conclusions 444
Acknowledgements 444
References 444
11 Gd-Containing Nanoparticles as MRI Contrast Agents 449
Klaas Nicolay, Gustav Strijkers, and Holger Gr¨ull
11.1 Introduction 449
11.2 Length scales and excretion pathways 452
11.3 Preparation of Gd-containing nanoparticles 454
11.4 Methods for nanoparticle characterization 460
11.5 In vitro applications 468
11.6 In vivo applications 475
11.7 Conclusions and future perspectives 481
Acknowledgements 483
References 483
Index 489
