Metal Ions in Bio-Imaging Techniques
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Metal Ions in Bio-Imaging Techniques

Astrid Sigel, Eva Freisinger, Roland K.O. Sigel, Astrid Sigel, Eva Freisinger, Roland K.O. Sigel

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eBook - ePub

Metal Ions in Bio-Imaging Techniques

Astrid Sigel, Eva Freisinger, Roland K.O. Sigel, Astrid Sigel, Eva Freisinger, Roland K.O. Sigel

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About This Book

Volume 22, entitled Metal Ions in Bio-Imaging Techniques, of the series Metal Ions in Life Sciences deals with metal ions as tools in imaging. This dates back to the first half of the past century, when barium sulfate was orally given to patients undergoing X-ray examination. The use of contrast agents has since developed into a large interdisciplinary field encompassing not only medicine, but also chemistry, material sciences, physics, biology, engineering, and computer sciences. MILS-22 provides deep and current insights in 17 stimulating chapters on the new research frontiers of this fast growing field on bio-imaging... and beyond. For example, adding bio-sensing yields theranostic agents, meaning diagnosis and therapy linked in the same molecule; ions of Gd, Mn, Fe, Co, Ir, 99m Tc, etc., are involved. Other important topics are, e.g., metal complexes in paramagnetic Chemical Exchange Transfer (paraCEST), radiometals for Positron Emission Tomography (PET) imaging, or paramagnetic metal ion probes for 19 F magnetic resonance imaging. MILS-22 is written by 57 internationally recognized experts from 12 countries, that is, from the US via Europe to China. The impact of this vibrant research area is manifested by more than 2300 references and nearly 120 figures, mostly in color, and several informative tables. To conclude, Metal Ions in Bio-Imaging Techniques is an essential resource for scientists working in the wide range from material sciences, enzymology, analytic, organic, and inorganic biochemistry all the way through to medicine including the clinic... not forgetting that also excellent information for teaching is provided.

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De Gruyter

1 Metal Ions in Bio-Imaging Techniques: A Short Overview

PhD Sergey Shuvaev
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
The Institute for Innovation in Imaging, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA <[email protected]>
PhD Peter Caravan
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA


Endogenous metal ions play a pivotal role in many biological systems, ranging from transition metal cofactors in essential enzymes to calcium ions in bones and cartilages. The idea of using exogenous metal ions as a diagnostic tool dates back to the first half of the 20th century when barium salts were orally administered to patients undergoing X-ray examination. Since that time, the field of molecular imaging has experienced remarkable changes, driven by the technological advances offered by modern imaging techniques. Each year brings hundreds of new molecular probes that are reported in preclinical studies and a few dozen enter human clinical trials. Such a massive data flow requires an appropriate classification, both by the type of imaging modality and chemical structure of the molecular probe. In this introductory chapter, recent advances and challenges in metal-based molecular imaging are discussed in four individual sections, covering magnetic resonance imaging (MRI), the nuclear medicine techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT), X-ray computed tomography (CT), and luminescent imaging, while a final section is dedicated to multimodal imaging, encompassing probes that can simultaneously produce a diagnostic signal detected by more than one imaging mode. Each of these sections, in turn, is subdivided into several parts, each dealing with a particular class of molecular probes based on their chemical structure, as well as the combination of imaging with therapy. We highlight representative examples of the different types of probes.
Keywords: imaging · magnetic resonance imaging · molecular probe · positron emission tomography · radiotracer,

1. Introduction

The advent of modern-day clinical diagnostic tools has revolutionized the healthcare system. A wide range of imaging modalities, now routinely available to patients, allows rapid and accurate diagnosis and prognosis, significantly improving the quality of medical care. However, the full potential of imaging techniques would never be unleashed without the aid of the chemistry community, who have immensely contributed by developing various types of molecular probes administered to patients during a radiological procedure. As imaging instrumentation and technology advance, so do the molecular probes, pushing the limits of imaging modalities. Fresh insights into biochemical mechanisms help to identify new molecular targets for imaging probes with higher specificity towards a particular pathology.
2019 marked the 150th anniversary of the Periodic Table of the Elements, a construct that still remains by far the most convenient layout to group and analyze the elements for a specific application. Metals comprise the majority of known elements, whose unique properties make them essential for virtually all biological systems, including the most advanced and sophisticated one – humankind – who eventually adapted metal ions to create molecular tools to study the biological processes behind their own existence. In the realm of molecular imaging, there are strong correlations between an exerted functional property and the element’s position in the periodic table. Metal complexes of biologically endogenous first-row transition metal ions, such as Mn2+/3+ and Fe2+/3+, have been extensively studied as potential alternatives to gadolinium-based contrast agents, while their heavier cousins from the platinum-group are well known to form very stable and bright luminescent complexes used for cellular staining and photodynamic therapy. Externally shielded f orbitals in lanthanides engender truly unique optical and magnetic properties, prompting their use as magnetic resonance imaging (MRI) and fluorescent probes, while their remarkable chemical stability also sparked interest in the production of their radioisotopes suitable for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging.
Despite continuing advances, each imaging modality has its own limitations, and these limitations have tempted researchers to create multimodal probes that can take advantage of several imaging techniques. Although still nascent, the field of multimodal imaging has experienced a rapid growth in the past few years and is expected to continue a steady rise, approaching clinical practice. At the same time, combining diagnostic and therapeutic modalities within a single molecule is of great value in the emerging era of personalized medicine.

2. Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy Probes

2.1. Recent Advances in Gadolinium-Based Probes

Gadolinium-based contrast agents (GBCAs) represent one of the most widely prescribed class of drugs and by far the largest administered metal-based drug with over 30 million administrations per year worldwide [1]. About 40 % of all MRI scans employ a GBCA which is required for diagnosis, staging, or monitoring treatment across a range of pathologies from cancer to cardiovascular disease to neurological disorders. There have been nine different GBCAs approved for clinical use, including 6 linear (acyclic) and 3 macrocyclic chelates (Figure 1), although some of these have been withdrawn from the market. Over the last decade, safety concerns have been mounting in connection to clear evidence that gadolinium can cause a devastating syndrome called nephrogenic systemic fibrosis in patients with impaired renal function [2], and that some Gd is retained in the body in all patients and that this retention is cumulative with cumulative dosing. Despite initial claims to the contrary, even the more kinetically inert macrocyclic GBCAs are clearly retained in patients, although likely to a lesser extent than the line...

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