Responsive Magnetic Resonance Imaging Contrast Research Articles

A Bioinspired Cu2+-Responsive Magnetic Resonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity.

Imaging extracellular Cu2+ in vivo is of paramount interest due to its biological importance in both physiological and pathological states. Magnetic resonance imaging (MRI) is a powerful technique to do so. However, the development of efficient MRI contrast agents selective for Cu2+, particularly versus the more abundant Zn2+ ions, is highly challenging. We present here an innovative Cu2+-responsive MRI contrast agent that contains a bioinspired Cu2+ binding site. This sensor shows a remarkable increase in relaxivity of nearly 400% in the presence of Cu2+, which could be rationalized in terms of an increase in the hydration number of the Ln3+ ion, as demonstrated by spectroscopic and relaxometric studies and supported by density functional theory calculations. Importantly, the system also shows an unprecedented selectivity for Cu2+, in particular over Zn2+. Phantom MRI images were recorded at 9.4 T to highlight the potential of such probes, which lies directly in their bioinspired design.

A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver In Vivo.

The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL1) has high selectivity for copper ions and exhibits a 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (XAS) studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson's disease.

Aspects of structural order in 209Bi-containing particles for potential MRI contrast agents based on quadrupole enhanced relaxation

ABSTRACTQuadrupole relaxation enhancement (QRE) has been suggested as the key mechanism for a novel class of field-selective, potentially responsive magnetic resonance imaging contrast agents. In previous publications, QRE has been confirmed for solid compounds containing 209Bi as the quadrupolar nucleus (QN). For QRE to be effective in aqueous dispersions, several conditions must be met, i.e. high transition probability of the QN at the 1H Larmor frequency, water exchange with the bulk and comparatively slow motion of the Bi-carrying particles. In this paper, the potential influence of structural order within the compounds (‘crystallinity’) on QRE was studied by nuclear quadrupole resonance (NQR) spectroscopy in one crystalline and two amorphous preparations of Triphenylbismuth (BiPh3). The amorphous preparations comprised (1) a shock-frozen melt and (2) a granulate of polystyrene which contained homogeneously distributed BiPh3 after common dissolution in THF and subsequent evaporation of the solvent. In contrast to the crystalline powder which exhibits strong, narrow NQR peaks the amorphous preparations did not reveal any NQR signals above the noise floor. From these findings, we conclude that the amorphous state leads to a significant spectral peak broadening and that for efficient QRE in potential contrast agents structures with a high degree of order (near crystalline) are required.

Tunable Performance of Manganese Oxide Nanostructures as MRI Contrast Agents.

The development of responsive magnetic resonance imaging contrast agents opens the door to a highly sensitive and specific diagnosis of altered physiological conditions. In this field, manganese dioxide (MnO2 ) is starting to be a leading contributor due to its susceptibility to conditions relevant to human diseased states, such as cancer. So far, the preclinical application of MnO2 has mainly been in the form of nanosheets, with enhancements of magnetic resonance imaging signals up to 50-fold upon activation. Herein, we thoroughly investigate, through a simple reaction, a series of Mnx Oy samples and correlate their phase composition and structure/morphology to the performance as classic/responsive MRI contrast agents in response to redox changes. Signal enhancements as high as 140-fold were obtained from MnO2 nano-urchins, and their capability as responsive magnetic resonance imaging contrast agents was demonstrated in vitro.

Promising strategies for Gd-based responsive magnetic resonance imaging contrast agents

Magnetic resonance imaging is a powerful imaging modality that is often coupled with paramagnetic contrast agents based on gadolinium to enhance sensitivity and image quality. Responsive contrast agents are key to furthering the diagnostic potential of MRI, both to provide anatomical information and to discern biochemical activity. Recent design of responsive gadolinium-based T₁ agents has made interesting progress, with the development of novel complexes which sense their chemical environment through changes in the coordination of water molecules, the molecular tumbling time or the number of metal centres. Particular promising design strategies include the use of multimeric systems, and the development of dual imaging probes.

ChemInform Abstract: Responsive Magnetic Resonance Imaging Contrast Agents as Chemical Sensors for Metals in Biology and Medicine

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine

This tutorial review highlights progress in the development of responsive magnetic resonance imaging (MRI) contrast agents for detecting and sensing biologically relevant metal ions. Molecular imaging with bioactivatable MRI indicators offers a potentially powerful methodology for studying the physiology and pathology of metals by capturing dynamic three-dimensional images of living systems for research and clinical applications. This emerging area at the interface of inorganic chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from coordination chemistry and spectroscopy to supramolecular chemistry and molecular recognition to metals in biology and medicine.