Metalloprotein‐based MRI probes

Matsumoto, Yuri; Jasanoff, Alan

doi:10.1016/j.febslet.2013.01.044

Cited by 23 publications

(16 citation statements)

References 125 publications

(146 reference statements)

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“…Previous efforts to develop such reporters have focused primarily on two classes of proteins. In one class, metalloproteins and metal ion transporters are overexpressed to enrich the paramagnetic content of cells, thereby enhancing nuclear relaxation rates and producing contrast in T 1 - or T 2 -weighted MRI91213141516171819252627. In the second strategy, proteins with large numbers of basic or acidic amino acids are used to generate contrast through chemical exchange saturation transfer (CEST) between protein-bound and aqueous protons68212228.…”

mentioning

confidence: 99%

Non-invasive imaging using reporter genes altering cellular water permeability

Mukherjee

Davis

et al. 2016

Nat Commun

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Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

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confidence: 99%

Non-invasive imaging using reporter genes altering cellular water permeability

Mukherjee

Davis

et al. 2016

Nat Commun

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“…Contrast agents such as iron oxide [7], gadolinium [8] and metalloproteins [9] are commonly used to increase the MR contrast of biological structures. These agents function by X-ray attenuation or magnetic resonance signal enhancement by highlighting tissues or cells that otherwise would be difficult to delineate from their surroundings.…”

Section: Introductionmentioning

confidence: 99%

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung

Murphy

Hale

Reid

et al. 2016

Methods

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Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a ‘proof-of-concept’ experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course.

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“…Native metalloproteins or engineered metal binding proteins have been used to develop MRI contrast agents [28]. Metalloproteins such as hemoglobin and the heme domain of cytochrome P450 BM3 containing paramagnetic metal ions (Cu 2+ , Fe 2+ , Fe 3+ , Mn 2+ , and Mn 3+ ) with spin quantum numbers from 1/2 to 5/2 have been applied to probe brain activities [28, 29].…”

Section: Introductionmentioning

confidence: 99%

“…Metalloproteins such as hemoglobin and the heme domain of cytochrome P450 BM3 containing paramagnetic metal ions (Cu 2+ , Fe 2+ , Fe 3+ , Mn 2+ , and Mn 3+ ) with spin quantum numbers from 1/2 to 5/2 have been applied to probe brain activities [28, 29]. Paramagnetic transition metal ions can be caged in ferritin as T2-weighted MRI contrast agents [30, 31].…”

Section: Introductionmentioning

confidence: 99%

Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents

Qiao

Xue

et al. 2013

J Biol Inorg Chem

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Epidermal growth factor receptor (EGFR) and HER2 are major prognosis biomarkers and drug targets overexpressed in various types of cancer cells. There is a pressing need to develop MRI contrast agents capable of enhancing the contrast between normal tissues and tumors with high relaxivity, capable of targeting tumors, and with high intratumoral distribution and minimal toxicity. In this review, we first discuss EGFR signaling and its role in tumor progression as a major drug target. We then report our progress in the development of protein contrast agents with significant improvement of both r1 and r2 relaxivities, pharmacokinetics, in vivo retention time, and in vivo dose efficiency. Finally, we report our effort in the development of EGFR-targeted protein contrast agents with the capability to cross the endothelial boundary and with good tissue distribution across the entire tumor mass. The noninvasive capability of MRI to visualize spatially and temporally the intratumoral distribution as well as quantify the levels of EGFR and HER2 would greatly improve our ability to track changes of the biomarkers during tumor progression, monitor treatment efficacy, aid in patient selection, and further develop novel targeted therapies for clinical application.

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Metalloprotein‐based MRI probes

Cited by 23 publications

References 125 publications

Non-invasive imaging using reporter genes altering cellular water permeability

Non-invasive imaging using reporter genes altering cellular water permeability

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung

Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents

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