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Keywords = metal ion-responsive MRI agents

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13 pages, 2048 KB  
Article
The Development of a Smart Magnetic Resonance Imaging and Chemical Exchange Saturation Transfer Contrast Agent for the Imaging of Sulfatase Activity
by Ilse M. Welleman, Friederike Reeβing, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Ben L. Feringa and Wiktor Szymanski
Pharmaceuticals 2023, 16(10), 1439; https://doi.org/10.3390/ph16101439 - 11 Oct 2023
Cited by 5 | Viewed by 3099
Abstract
The molecular imaging of biomarkers plays an increasing role in medical diagnostics. In particular, the imaging of enzyme activity is a promising approach, as it enables the use of its inherent catalytic activity for the amplification of an imaging signal. The increased activity [...] Read more.
The molecular imaging of biomarkers plays an increasing role in medical diagnostics. In particular, the imaging of enzyme activity is a promising approach, as it enables the use of its inherent catalytic activity for the amplification of an imaging signal. The increased activity of a sulfatase enzyme has been observed in several types of cancers. We describe the development and in vitro evaluation of molecular imaging agents that allow for the detection of sulfatase activity using the whole-body, non-invasive MRI and CEST imaging methods. This approach relies on a responsive ligand that features a sulfate ester moiety, which upon sulfatase-catalyzed hydrolysis undergoes an elimination process that changes the functional group, coordinating with the metal ion. When Gd3+ is used as the metal, the complex can be used for MRI, showing a 25% decrease at 0.23T and a 42% decrease at 4.7T in magnetic relaxivity after enzymatic conversion, thus providing a “switch-off” contrast agent. Conversely, the use of Yb3+ as the metal leads to a “switch-on” effect in the CEST imaging of sulfatase activity. Altogether, the results presented here provide a molecular basis and a proof-of-principle for the magnetic imaging of the activity of a key cancer biomarker. Full article
(This article belongs to the Special Issue Next-Generation Contrast Agents for Medical Imaging)
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17 pages, 2287 KB  
Review
Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents
by Pooyan Khalighinejad, Daniel Parrott and A. Dean Sherry
Pharmaceuticals 2020, 13(10), 268; https://doi.org/10.3390/ph13100268 - 24 Sep 2020
Cited by 14 | Viewed by 4647
Abstract
Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the [...] Read more.
Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the most commonly used agents in both the clinical and research environments. Zinc is an essential element involved with over 3000 different cellular proteins, and disturbances in tissue levels of zinc have been linked to a wide range of pathologies, including Alzheimer’s disease, prostate cancer, and diabetes mellitus. MR contrast agents that respond to the presence of Zn2+ in vivo offer the possibility of imaging changes in Zn2+ levels in real-time with the superior spatial resolution offered by MRI. Such responsive agents, often referred to as smart agents, are typically composed of a paramagnetic metal ion with a ligand encapsulating it and one or more chelating units that selectively bind with the analyte of interest. Translation of these agents into clinical radiology is the next goal. In this review, we discuss Gd3+-based MR contrast agents that respond to a change in local Zn2+ concentration. Full article
(This article belongs to the Special Issue Next Generation of MRI Agents)
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