Lanthanide and Other Transition Metal Ion Complexes and Nanoparticles in Magnetic Resonance Imaging (Metal Ions in Life Sciences Series)

Cover
Title Page
Copyright Page
About the Editors
Historical Development and Perspectives of the Series
Preface to Volume 27
Table of Contents
Contributors to Volume 27
Handbooks and Book Series Published and (Co‑)edited by the SIGELs
Chapter 1 Synthesis and Characterization of Ligands and their Gd(III) Complexes
	1 Introduction
	2 Physicochemical Properties of GBCAs: Thermodynamic, Inertness, and Relaxometry
	3 “DOTA‑like” Derivatives and Related DOTA‑Compounds Based on the Cyclen Platform
		3.1 Ways to Improve “DOTA”
			3.1.1 Number of Water Molecules in the First Coordination Sphere of the Metal Ion
			3.1.2 Improvement of the Rotational Correlation Time of DOTA Derivatives
			3.1.3 Residence Time in the First Coordination Sphere
		3.2 DO3A and DO3A‑Based Derivatives
			3.2.1 DO3A and DO3A‑Based Derivatives Synthesis
			3.2.2 DO3A and DO3A‑Based Derivatives Properties
		3.3 DO2A or DO2PA Derivatives
			3.3.1 DO2A or DO2PA Derivatives Synthesis
			3.3.2 DO2A or DO2PA Derivative Properties
	4 Cyclen‑Based Gd[sup(3+)] Chelators with 4 Identical Pendant Arm Other Than Acetate
		4.1 Synthesis
		4.2 Properties
	5 Backbon‑Modified DOTA Derivatives
	6 13‑4‑Ane and Cyclam Derivatives
	7 Tacn‑Based Gadolinium(III) Chelators
		7.1 Synthesis
		7.2 Thermodynamic Stability
		7.3 Relaxivity
	8 Pyclen‑Based Chelators as GBCAs
		8.1 H[sub(3)]PCTA: The Archetype of Pyclen‑Based Chelators
			8.1.1 Synthesis
			8.1.2 Physicochemical and Relaxometric Properties of [Gd(PCTA)]
		8.2 PCTA Derivatives
			8.2.1 Synthesis of PCTA Derivatives
			8.2.2 Thermodynamic and Kinetic Stability
			8.2.3 Relaxometric Properties
	9 Conclusion
	Abbreviations and Definitions
	References
Chapter 2 PARASHIFT Systems: Including [sup(19)]F Effects
	1 Introduction
		1.1 Sensitivity Limitations of Traditional MR Chemical Shift Approaches
		1.2 Overcoming the MR Sensitivity Limitation
	2 Effects of Paramagnetic Ions on Magnetic Resonance
		2.1 Chemical Shift
		2.2 Relaxation
	3 Ln(III)-Based PARASHIFT Agents
		3.1 Ln(III)-Based [sup(19)]F PARASHIFT Systems
		3.2 Ln(III)-Based [sup(1)]F PARASHIFT Systems
		3.3 Applications of Ln(III) PARASHIFT Systems
			3.3.1 Temperature Sensitivity
			3.3.2 pH-Responsive Probes
			3.3.3 Ion-Responsive Probes
			3.3.4 Enzyme-Responsive Probes
	4 Transition Metal-Based PARASHIFT Agents
		4.1 TM-Based [sup(19)]F PARASHIFT Systems
		4.2 TM-Based [sup(1)]H PARASHIFT Systems
		4.3 Applications of TM-Based PARASHIFT Systems
			4.3.1 Temperature Sensitivity
			4.3.2 pH-Responsive Probes
			4.3.3 Redox Active Probes
			4.3.4 Spin State-Responsive Probes
	5 Concluding Remarks and Future Directions
	Abbreviations and Definitions
	References
Chapter 3 Targeted MRI Contrast Agents
	1 Introduction
	2 Tumors
		2.1 General Tumor Targeting
			2.1.1 Enhanced Permeability and Retention Effect
			2.1.2 Epidermal Growth Factor Receptor
			2.1.3 Integrin α[sub(v)]β[sub(3)] Receptors
			2.1.4 Folate Receptors
			2.1.5 Other Receptors
		2.2 Liver Tumor Targeting
			2.2.1 Folate
			2.2.2 Organic Anion-Transporting Polypeptide 1
			2.2.3 Chemokine Receptor 4
		2.3 Brain Tumor Targeting
			2.3.1 Integrin α[sub(v)]β[sub(3)] Receptors
			2.3.2 Folic Acid Receptors
			2.3.3 D-Glucose
			2.3.4 Interleukin-13 Receptor Subunit Alpha-2
		2.4 Breast Tumor Targeting
		2.5 Ovarian Tumor Targeting
		2.6 Prostate Tumor Targeting
	3 Liver
		3.1 Organic Anion-Transporting Polypeptide 1
		3.2 Fibrin
		3.3 Collagen
	4 Brain
	5 Lung
	6 Other Targets
		6.1 Blood Targeting
		6.2 Elastin and Tropoelastin
	7 Conclusions
	Acknowledgment
	Abbreviations and Definitions
	References
Chapter 4 Responsive MRI Contrast Agents
	1 Temperature Sensing
	2 Ion-Responsive Contrast Agents
		2.1 Calcium
		2.2 Zinc
		2.3 Copper
	3 pH-Responsive Probes
	4 Neurotransmitter Detection
	5 Enzymatically Responsive Contrast Agents
	6 Redox-Responsive Contrast Agents
	7 Quantification Methods
	Abbreviations and Definitions
	References
Chapter 5 Mn-Based Small Complexes as MRI Contrast Agents
	1 Introduction
	2 Manganese(II) Chelates
		2.1 Open-Chain Manganese(II) Complexes
		2.2 Macrocyclic Manganese(II) Complexes
		2.3 Bispidine Manganese(II) Complexes
	3 Manganese(III) Complexes
	4 Molecular Imaging Based on Manganese Complexes
		4.1 pH Detection
		4.2 Zinc Detection
		4.3 Redox Detection
		4.4 Redox Detection in [sup(19)]F MRI
		4.5 Protein Targeting
	5 General Conclusions
	Acknowledgments
	Abbreviations and Definitions
	References
Chapter 6 Other First-Row Transition Metal-Based Complexes as MRI Contrast Agents
	1 Introduction
	2 Transition Metal Relaxivity Agents
		2.1 Mechanisms of Proton Relaxation by Paramagnetic Metal Ions
		2.2 Considerations Specific to Fe(III) MRI Probes
		2.3 Classes of Fe(III) Complexes
		2.4 Additional First-Row Transition Metal Probes
	3 Transition Metal ParaCEST Agents
		3.1 Basic Theory for ParaCEST Agents
		3.2 Other Considerations for ParaCEST Agents
		3.3 Classes of ParaCEST Agents
		3.4 ParaCEST Agents Responsive to pH, Temperature, or Redox
			3.4.1 ParaCEST Agents as pH-Responsive Probes
			3.4.2 Temperature-Responsive ParaCEST Probes
			3.4.3 Redox-Responsive ParaCEST Agents
		3.5 Toward In Vivo Applications of ParaCEST Agents
	4 General Conclusions
	Acknowledgments
	Notes
	Abbreviations and Definitions
	References
Chapter 7 Lanthanide-Based Paramagnetic Chemical Exchange Saturation Transfer (paraCEST) Agents for MRI
	1 Introduction
		1.1 The Discovery of paraCEST Agents
		1.2 Impact of Water Proton T[sub(1)] on CEST Intensity
	2 Factors Affecting Ln-H[sub(2)]O Exchange Rates
		2.1 Nature of the Ligating Group
		2.2 Coordination Geometry in LnDOTA-Type Chelates
		2.3 Cation Size
		2.4 Coordination Isomer Selection through Stereochemical Effects
		2.5 Impact of Amide Substituents
		2.6 Impact of Amide Substituent Orientation
	3 Responsive paraCEST Agents and Ratiometric Methods
		3.1 Redox Sensor
		3.2 pH Sensor
		3.3 Glucose and Zn[sup(2+)] Sensors
		3.4 Ratiometric CEST
		3.5 paraCEST Agents for Detection of Enzyme Activity
		3.6 paraCEST Agents for Imaging Extracellular pH (pH[sub(e)]) In vivo
		3.7 Metabolite Specific CEST Detection of D- and L-Lactate
	4 Summary and Conclusions
	Acknowledgments
	References
Chapter 8 LipoCEST and Similar Systems
	1 Introduction
	2 NMR/MRI and Compartments
	3 LipoCEST: Liposomes Encapsulating Lanthanide Shift Reagents
	4 An Analytical Assay Based on LipoCEST Agents
	5 Giant LipoCEST
	6 Lipo-ParaCEST: Liposomes Encapsulating ParaCEST Agents
	7 CellCEST: Living Compartments Encapsulating Lanthanide Shift Reagents
	8 Combined Use of LipoCEST and RBCs
	9 Conclusions
	Abbreviations and Definitions
	References
Chapter 9 Superparamagnetic Iron Oxide and Ferrite Nanoparticles for MRI
	1 Introduction
	2 Superparamagnetic Relaxation Theory
		2.1 Longitudinal Relaxation
		2.2 Transverse Relaxation
	3 SPION-Based Contrast Agents
		3.1 Clinically-Developed SPION-Based Contrast Agents
			3.1.1 Hepatic MRI
			3.1.2 Lymph Node Imaging
			3.1.3 Blood-Pool Imaging
			3.1.4 Gastrointestinal Imaging
			3.1.5 T[sub(2)]-Weighted MRI with SPION
		3.2 SPION as T[sub(1)] Contrast Agents
			3.2.1 Parameters Affecting T[sub(1)] Contrast with SPION
			3.2.2 T[sub(1)]-Weighted MRI with SPION
	4 General Conclusions
	Abbreviations and Definitions
	References
Chapter 10 Ln-Based Particles as MRI Contrast Agents
	1 Introduction
	2 Lanthanide Oxides and Salts as MRI Contrast Agents
		2.1 Gd Oxides and Inorganic Gd Salts as T[sub(1)] MRI Contrast Agents
		2.2 Polysiloxanes Grafted with Ln-Chelates (AGuIX) for Image-Guided Therapy
		2.3 Dy[sub(2)]O[sub(3)], Ho[sub(2)]O[sub(3)], NaDyF[sub(4)], and NaHoF[sub(4)] as T[sub(2)] Contrast Agents
		2.4 Gd-Based NPs as Dual T[sub(1,2)] MRI Contrast Agents
		2.5 Ho-Based Microspheres for Image-Guided Embolization Therapy
	3 Ln[sup(3+)]-Loaded Porous Silicates
		3.1 Ln[sup(3+)]-Loaded Mesoporous Systems
		3.2 Ln[sup(3+)]-Loaded Zeolites
	4 General Conclusions
	Abbreviations and Definitions
	References
Chapter 11 Manganese- and Iron-Based Nanoparticles as MRI Contrast Agents
	1 Introduction
	2 Manganese-Based Nanoparticles as MRI Contrast Agents
		2.1 Non-Mn(II) Oxide Systems
			2.1.1 Non-MnO Mn(II) Systems-Based Nanoparticles
			2.1.2 Non-Mn[sub(3)]O[sub(4)] Mn(III) Systems-Based Nanoparticles
			2.1.3 Non-MnO[sub(2)] Mn(IV) Systems-Based Nanoparticles
		2.2 Mn Oxides
			2.2.1 MnO Nanoparticles
			2.2.2 Mn[sub(3)]O[sub(4)] Nanoparticles
			2.2.3 MnO[sub(2)] Nanoparticles
	3 MRI T[sub(1)] Contrast Agents Based on Iron(III) Nanosystems
		3.1 Nanoparticles Based on Amphiphilic Polymeric Matrices
		3.2 Nanosystems Based on Polyphenolic Units
		3.3 Nanoparticles Containing Mixed Metals
		3.4 Miscellaneous Nanoparticles
	4 General Conclusions
	Acknowledgments
	Abbreviations and Definitions
	References
Chapter 12 Advances in PET/MRI and Probe Development for Biomedical Precision Imaging Applications
	1 Advanced Imaging Techniques
	2 Current Status of Monomodal Imaging Techniques
	3 Multimodal Imaging Techniques
		3.1 PET/CT
		3.2 PET/MRI
			3.2.1 Current Implementation of Clinical PET/MRI Scanners
	4 PET/MRI Contrast Agents
		4.1 Basic Concepts
		4.2 Rationale and Challenges for Bimodal PET/MRI Contrast Agents
			4.2.1 Small Molecules
			4.2.2 Nanoparticles
			4.2.3 Quantitative Imaging
		4.3 Small Molecules vs Nanoparticles
			4.3.1 Small Molecules
			4.3.2 Nanoparticles
		4.4 Preparation of Bimodal PET/MRI Contrast Agents
			4.4.1 Low Molecular Bimodal PET/MRI Contrast Agents
			4.4.2 Nanoparticles
	5 Current Preclinical Applications of PET/MRI Contrast Agents
		5.1 Cardiovascular Applications
		5.2 Imaging Infection and Inflammation
		5.3 Oncology
		5.4 Neuroimaging
	6 Conclusions
	Acknowledgments
	References
Index