Preface to Volume 22 Metal Ions in Bio-Imaging Techniques

Endogenous metal ions play crucial roles in biological systems, ranging from transition metal cofactors in essential enzymes to calcium ions in bones and cartilages. The use of exogenous metal ions as tools dates back to the first half of the past century when barium sulfate was orally given to patients undergoing X-ray examination. Since then, molecular imaging has experienced remarkable changes due to the technical advances. The Introductory Chapter of the 22nd volume of the series Metal Ions in Life Sciences (MILS) is setting the scene by providing an overview of the metal ions and methods used today in the field of bio-imaging. Gadolinium(III)-based Contrast Agents (GBCAs) have been extensively used in Magnetic Resonance Imaging (MRI) in clinical practice since 1988 because they improve the contrast between healthy and diseased tissues. This success story seemed to come to a halt in 2006 when Nephrogenic Systemic Fibrosis (NSF) was linked to the administration of linear GBCAs in a small subset of patients with poor kidney function. This and the observed deposition of Gd(III) in various tissues (brain, bone) raised concerns about the safety of GBCAs. The attempts to overcome these side effects and the re-appraisal of GBCAs are summarized in Chapter 2. Manganese(II) is an essential element with 5 unpaired electrons, slow electron spin relaxation, and fast water exchange. Mn2C is an excellent nuclear probe and the most promising alternative to replace Gd(III) in contrast agents (CAs) for MRI though there are handicaps due to the labile nature of Mn2C. Yet, in the last decade much data has accumulated, which allows establishing relationships between the structure of Mn2C complexes and their stability, inertness, and relaxation properties. Despite the endogenous nature of Mn2C, in high concentrations it is neurotoxic and therefore, Mn2C also needs to be protected like Gd(III) (Chapter 3). Finally, high-spin Mn3C is also a good relaxation agent and indeed, Mn3C complexes were investigated as MRI probes.