A snapshot of the vast array of diamagnetic CEST MRI contrast agents

Abstract

Since the inception of CEST MRI in the 1990s, a number of compounds have been identified as suitable for generating contrast, including paramagnetic lanthanide complexes, hyperpolarized atom cages and, most interesting, diamagnetic compounds. In the past two decades, there has been a major emphasis in this field on the identification and application of diamagnetic compounds that have suitable biosafety profiles for usage in medical applications. Even in the past five years there has been a tremendous growth in their numbers, with more and more emphasis being placed on finding those that can be ultimately used for patient studies on clinical 3 T scanners. At this point, a number of endogenous compounds present in tissue have been identified, and also natural and synthetic organic compounds that can be administered to highlight pathology via CEST imaging. Here we will provide a very extensive snapshot of the types of diamagnetic compound that can generate CEST MRI contrast, together with guidance on their utility on typical preclinical and clinical scanners and a review of the applications that might benefit the most from this new technology.

Key Insights on the Classification and Theranostic Applications of Magnetic Resonance Imaging Contrast Agents

“…Various CEST agents containing exchangeable protons such as endogenous proteins, glycogen, glutamate, creatine, L-arginine, glucose, and barbituric acid have been investigated as diagnostic non-invasive biomarkers in MRI examinations. [63][64][65][66][67] Several drugs such as gemcitabine, citicoline, olsalazine have also been used for developing CEST MRI agents. In addition to this, iodinated X-ray contrast agents such as iopromide, iopamidol, iodixanol, ioversol, iobitridol, and iohexol based CEST agents have also been successfully used in multiple clinical applications (Figure 4).…”

Label-Free Chemically and Molecularly Selective Magnetic Resonance Imaging

“…Therefore, exchangeable protons in the mM concentration range would result in a few percent change of water signal that makes it readily detectable. As such, a wide variety of biomolecules with such or similar diamagnetic properties have been explored and discussed in our recent review papers. − Given its capability of chemically selective imaging, CEST MRI has become an attractive molecular imaging method increasingly explored for investigating the disease-associated changes in the tissue that are not informed through structural MRI and MRS. While DWI provides structural and mechanical properties of the cells and tissue, tissue properties and their changes probed by CEST imaging are more relevant to tissue biological and physiological conditions.…”

Special issue on chemical exchange saturation transfer MRI

“…Importantly, Longo et al review and identify diamagnetic compounds that have suitable biosafety profiles for use in medical applications. 10 Sherry et al address the factors that limit paraCEST sensitivity in vivo and offer insights on how to dramatically increase this sensitivity.…”

“…Overviews of diaCEST, paraCEST, and compartmentalized agents are given by Longo et al, 10 Sherry et al, 11 and Ferrauto and Terreno 12 respectively. Importantly, Longo et al review and identify diamagnetic compounds that have suitable biosafety profiles for use in medical applications 10 .…”

“…Overviews of diaCEST, paraCEST, and compartmentalized agents are given by Longo et al, 10 Sherry et al, 11 and Ferrauto and Terreno 12 respectively. Importantly, Longo et al review and identify diamagnetic compounds that have suitable biosafety profiles for use in medical applications 10 . Sherry et al address the factors that limit paraCEST sensitivity in vivo and offer insights on how to dramatically increase this sensitivity.…”