Preface

The field of contrast agents for magnetic resonance imaging (MRI) has progressed by leaps and bounds over the last few decades, from metal complexes to responsive and targeted probes that enable multicolor imaging with remarkable resolution and sensitivity. Along the way, our understanding of the richness of the coordination chemistry of lanthanide and transition metals has grown tremendously, as has our ability to manipulate chemical and physical parameters to achieve new types of contrast. The complexity of the interactions of metal complexes and nanoparticles with biological systems and the uniqueness of their pharmacological properties is now widely appreciated.

As this field progresses quickly, the breadth of the techniques used in the synthesis and characterization of contrast agents can seem overwhelming. This book is not a classical review of the literature; many excellent reviews and books exist that serve that purpose. Rather, our intention is for this book to serve as a benchtop companion for chemists, physicists, and biologists. Throughout this book, different techniques that are used in the field of 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 interpret 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 information that is intended to help in the design of contrast agents to fill specific needs and guides readers through synthesis, characterization, evaluation, and determination of the chemical, physical, and biological properties of new contrast agents.

The first chapter of this book discusses the synthesis and characterization 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. Those studies are also discussed in the first chapter. Subsequent chapters detail the techniques relevant to specific classes of contrast agents: Gd^III-based contrast agents (Chapter 2), chemical exchange saturation transfer agents (Chapter 3), nanoparticle-based contrast agents (Chapter 4), transition-metal based T₁-shortening contrast agents (Chapter 5), and fluorine probes (Chapter 6). In each chapter, the principles underlying that class of contrast agent and the physical experiments uniquely suited to their studies are described. The book finishes with a chapter focused on biological and pharmacological experiments that are key to evaluating the potential of contrast agents for use in vivo.

This book would not have been possible without substantial contributions from the world-renowned experts who authored the chapters. To each of them, we offer our most sincere and largest possible thank you! We are especially indebted to Susan A. White, who downloaded, reviewed, and edited every single reference of this book. We also gratefully acknowledge Dr Sylvie Pailloux, who contributed to the editing of a few subchapters. Both of us thank our research groups for their patience as we spent time editing the book. More than anything, we are incredibly grateful for our families for their unwavering support throughout this journey.

To the reader, we hope this book will guide you through your own journey into the future of contrast agents for MRI.

Valérie C. Pierre and Matthew J. Allen