MRI Contrast Agents (eBook)

Dr. Sophie Laurent was born in 1967. Her studies were performed at the University of Mons-Hainaut (Belgium) where she received her PhD in Chemistry in 1993. She joined then Prof R.N. Muller’s team and was involved in the development (synthesis and physicochemical characterization) of paramagnetic Gd complexes and superparamagnetic iron oxide nanoparticles as contrast agents for MRI. She is currently working on the vectorization of contrast agents for molecular imaging. She is associate professor and co-author around 170 publications and more than 250 communications in international meetings.Dr. Dimitri Stanicki did his graduate work at the University of Mons (Ph.D. degree in 2010), where he achieved the synthesis of organic compounds for the treatment of parasitic diseases. In 2011, he joined R. Muller’s research group (MRI) where he started to develop new nanosystems for molecular imaging applications. He is the co-author of approximatively 10 publications, including a patent and a chapter book in the field of superparamagnetic contrast agents.Dr. Robert N. Muller, PhD in chemistry 1974 from the University of Mons-Hainaut where he was successively appointed Assistant, Lecturer and full Professor. Post-doctoral studies in Magnetic Resonance Imaging in Paul C. Lauterbur’s (2003 Nobel Prize in Medicine or Physiology) research group (MRI) at the State University of New York at Stony Brook in 1981-82 and sabbatical leave at the Center for Magnetic Resonance (CERM), Florence, Italy, in 2002-2003. He produced around 280 publications and 6 books. Currently Scientific Director of the Center for Microscopy and Molecular Imaging, Gosselies, Belgium.

Contents 6
1 Interest of Nanomaterials in Medicine 9
Abstract 9
References 10
2 Magnetic Properties 12
Abstract 12
2.1 Diamagnetic Substances 12
2.2 Paramagnetic Substances 13
2.3 Ferromagnetic Substances 13
2.4 Ferrimagnetic Substances 14
2.5 Antiferromagnetic Substances 14
2.6 Superparamagnetic Substances 14
References 17
3 Imaging Probes 19
Abstract 19
3.1 Magnetic Resonance Imaging (MRI) 19
3.1.1 Classical Description of NMR—Description on the Macroscopic Scale 21
3.1.2 NMR Signal Acquisition 23
3.1.3 Principle of MRI 24
3.1.3.1 Spatial Coding 24
3.1.3.2 Excitation Sequence 25
3.1.3.3 Contrast in MRI 25
3.2 MRI Contrast Agents 26
References 27
4 Paramagnetic Gadolinium Complexes 28
Abstract 28
4.1 Relaxation Mechanims of Gadolinium Complexes 30
4.1.1 Innersphere Mechanism 31
4.1.2 Outer-Sphere Mechanism 32
4.1.3 Second-Sphere Mechanism 33
4.1.4 Influence of the Different Parameters on the Innersphere and Outersphere Contributions 34
4.1.4.1 Innersphere Contribution 34
4.1.4.2 Outersphere Contribution 34
4.1.4.3 NMRD Profiles 35
4.2 Different Classes of Gadolinium Based MRI Contrast Agents 35
4.2.1 Vascular Contrast Agents 35
4.2.2 Smart Contrast Agents 36
4.2.2.1 PH Sensitive 36
4.2.2.2 Metal Sensitives 37
4.2.2.3 Enzyme-Activated Contrast Agents 39
4.2.2.4 pO2 41
4.2.3 Specific Contrast Agents for Molecular Imaging 41
4.2.4 How to Obtain High Relaxivity with Paramagnetic Gd-Derivatives by Increasing ?R 42
4.2.5 PARACEST Agents 48
References 50
5 Superparamagnetic Iron Oxide Nanoparticles 59
Abstract 59
5.1 Superparamgnetic Properties of Iron Oxide Nanoparticles 62
5.1.1 Relaxometric Properties 62
5.1.1.1 Relaxation Processes of Single Domain Iron Oxide Nanoparticles 62
5.1.1.2 Superparamagnetic Relaxation: Theoretical Model 64
5.1.1.3 Nuclear Magnetic Resonance Dispersion Profiles (NMRD) 68
5.2 Synthesis of Magnetic Nanoparticles 70
5.2.1 Coprecipitation Method 70
5.2.2 Hydothermal Method 72
5.2.3 Thermal Decomposition Method 73
5.2.4 Sol-Gel Methods 74
5.2.5 Microemulsions 75
5.2.6 Polyol Methods 76
5.2.7 Electrochemical Methods 76
5.2.8 Aerosol/Vapor Method 76
5.2.9 Sonolysis/Thermolysis 77
5.3 Stabilization of Nanoparticle Suspensions 77
5.3.1 Stability of Charged Nanoparticles 79
5.3.2 Steric Stabilization 84
5.3.3 The Surface of Iron Oxide Nanoparticles 84
5.3.4 Stabilization Strategies 88
5.3.4.1 Silica 90
5.3.4.2 Polymers 90
5.3.4.3 Small Organic Molecules 91
5.3.4.4 Biological Molecules 91
5.3.5 Recent Advances on the Stabilization of Hydrophobic Iron Oxide Nanoparticles 92
5.3.5.1 Stabilization by Ligand Addition 92
Polymers 93
Alkylammonium Salts 93
Lipids 95
5.3.5.2 Stabilization by Ligand Exchange 96
Small Charged Molecules 96
Polymers 96
Silica 99
References 103
6 MRI Applications: Classification According to Their Biodistribution 114
Abstract 114
6.1 Non-specific Agents (Interstitial Diffusion of Gadolinium Complexes) 115
6.1.1 Toxicity of Free Gadolinium and Gd-Complexes 115
6.1.2 NSF Disease [7–14] 117
6.2 Hepatic Agents 118
6.2.1 Gadolinium Complexes with Biliary Excretion: Gd-EOB-DTPA and Gd-BOPTA 118
6.2.2 Superparamagnetic Iron Oxide Nanoparticles as Specific Agents of Kupffer Cells 119
6.2.3 Contrast Agents for Lymphatic System 121
6.3 Vascular Contrast Agents 122
6.3.1 Superparamagnetic Nanoparticles 123
6.3.2 Macromolecular Contrast Agents (Albumin-Dextran, Polylysine-Gd-DTPA) 123
6.3.3 Applications 123
6.4 Conclusions 124
References 125