This book describes insight mechanisms for designing molecular probes and methods that these agents can be used for medical diagnosis in preclinical animal models via optical, MRI and PET imaging. The book has a wealth of schemes of synthesis and methods deduced from pioneers in the field, making it possible to immerse into real-world molecular imaging. Written for graduate student training and practitioners, this book will serve as a teaching material and/or reference for anyone interested in exploring the power of chemical synthesis of imaging agents.
Author(s): Wellington Pham
Publisher: Springer
Year: 2022
Language: English
Pages: 313
City: Singapore
Preface
Contents
1 Overview of the Fundamentals of Chemistry for Molecular Probe Design
1.1 Valence Bonding
1.2 Chemical Bonds of Molecular Probes in Biological System
1.2.1 Covalent Bonding
1.2.2 Hydrogen Bonding
1.2.3 Hydrophobic Interactions
1.2.4 Van Der Waals Forces
1.3 Terminology and Types of Reactions and Mechanisms
1.3.1 Terminology
1.3.2 Types of Chemical Reactions and Mechanisms
1.4 Useful Reaction Names for the Chemical Development of Molecular Probes
1.5 Conclusion
References
2 Principles for the Design of Fluorescent Dyes
2.1 Introduction
2.2 Xanthene Backbone Dyes
2.2.1 Rhodamine Dyes
2.2.2 Fluorescein Dyes
2.3 Cyanine Dyes
2.3.1 Merocyanine Dyes
2.3.2 Strategies to Fine-Tune the Near-Infrared Capabilities of Cyanine Dyes
2.3.3 Development of Near-Infrared Cyanine Dyes with a Large Stokes Shift
2.4 Non-fluorescent Near-Infrared Dyes
2.4.1 Azo Dyes
2.4.2 Azulene Dyes
2.5 BODIPY Dyes
2.6 Activated Dyes
2.7 Conclusion
References
3 Principles for the Design of PET Probes
3.1 Introduction
3.2 [18F] Labeling
3.2.1 Production of Fluorine-18 Radioisotopes
3.2.2 Methods of [18F]labeling
3.3 Methods of [11C] Labeling
3.3.1 Direct [11C]carboxylation
3.3.2 [11C]methylation
3.3.3 [11C]labeling via Carbonylation Using [11C]CO
3.4 Labeling via Prosthetic Chelators
3.4.1 Labeling Monoclonal Antibodies with [18F]F−
3.4.2 Labeling Monoclonal Antibodies with 64Cu
3.4.3 Labeling Peptides or Monoclonal Antibodies with 68Ga
3.5 Conclusion
References
4 Principles for the Design of MRI Probes
4.1 Introduction
4.2 Contrast Agents
4.2.1 Chelator-Free Metals
4.2.2 Chelator-Associated Metals
4.2.3 Hyperpolarized Contrast Agents
4.2.4 Superparamagnetic Nanoparticles
4.3 Conclusion
References
5 Solid-Phase Chemistry
5.1 Introduction
5.2 Solid Support Resins
5.2.1 Merrifield Resin
5.2.2 PAM Resin
5.2.3 MBHA and Rink MBHA Resins
5.2.4 Wang Resin
5.2.5 2-Chlorotrityl Resin
5.3 Resin Substitution
5.4 Solid-Phase Synthesis of Active Compounds and Dyes
5.4.1 Cyclic Peptides
5.4.2 Indole Analogs
5.4.3 Cyanine Dyes
5.4.4 Rhodamine Dyes
5.4.5 Fluorescein Dyes
5.4.6 Coumarin Dyes
5.4.7 BODIPY Dyes
5.4.8 Solvatochromic Dyes
5.4.9 Styryl Dyes
5.4.10 Dapoxyl Dyes
5.5 Conclusion
References
6 Construction of Molecular Probes and Imaging Applications
6.1 Introduction
6.2 Physical Information of Different Imaging Modalities
6.3 Targeted Imaging Approach
6.4 Imaging with Activatable Probes
6.5 Conclusion
References
