Current and potential imaging applications of ferumoxytol for magnetic resonance imaging
Oregon Health & Science University1, Duke University2, National Institutes of Health3, Lucile Packard Children's Hospital4, Semmelweis University5, University of California, Los Angeles6, University of New Mexico7, Harvard University8, University of Cambridge9, University of Colorado Denver10, Stanford University11, Siemens12, Veterans Health Administration13
TL;DR: The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging.
About: This article is published in Kidney International.The article was published on 2017-07-01 and is currently open access. It has received 216 citations till now. The article focuses on the topics: Ferumoxytol & Magnetic resonance imaging.
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TL;DR: The synthesis, surface functionalization and characterization of iron oxide nanoparticles, as well as their (pre‐) clinical use in diagnostic, therapeutic and theranostic settings, are summarized.
618 citations
Cites background from "Current and potential imaging appli..."
...Studies investigating the toxicity profile of ferumoxytol and ferumoxtran reported less than 1% of serious side effects (including anaphylatic shock, chest pain, dyspnea and hypotension) and 10–20% of moderate adverse events (such as back pain, headache and urticaria) [135,136]....
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TL;DR: Since ultrasmall superparamagnetic iron oxides are not associated with a risk of nephrogenic sclerosis, they can serve as a safer contrast agents compared with gadolinium chelates for MR angiography, tissue perfusion studies, and atherosclerotic plaque and tumor imaging.
Abstract: Since ultrasmall superparamagnetic iron oxides (USPIOs) are not associated with a risk of nephrogenic sclerosis, they can serve as a safer contrast agents compared with gadolinium chelates for MR angiography, tissue perfusion studies, and atherosclerotic plaque and tumor imaging; USPIOs are especially beneficial for patients with renal insufficiency or patients with uncertain creatinine laboratory values.
120 citations
TL;DR: While nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.
Abstract: The importance of medical imaging in the diagnosis and monitoring of cancer cannot be overstated. As personalized cancer treatments are gaining popularity, a need for more advanced imaging techniques has grown significantly. Nanoparticles are uniquely suited to fill this void, not only as imaging contrast agents but also as companion diagnostics. This review provides an overview of many ways nanoparticle imaging agents have contributed to cancer imaging, both preclinically and in the clinic, as well as charting future directions in companion diagnostics. We conclude that, while nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.
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TL;DR: The objective of this review is to outline current advances of nano-assemblies as remotely controlled DDSs, in hopes of accelerating the future development of intelligent nanomedicines.
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TL;DR: The motivations for using noncontrast MRA, potential contrast mechanisms, imaging techniques, advantages, and drawbacks with respect to CTA and CEMRA, and the level of evidence for using the various MRA techniques are considered.
Abstract: Both computed tomography (CT) angiography (CTA) and contrast-enhanced MR angiography (CEMRA) have proven to be useful and accurate cross-sectional imaging modalities over a wide range of vascular territories and vascular disorders. A key advantage of MRA is that, unlike CTA, it can be performed without the administration of a contrast agent. In this review article we consider the motivations for using noncontrast MRA, potential contrast mechanisms, imaging techniques, advantages, and drawbacks with respect to CTA and CEMRA, and the level of evidence for using the various MRA techniques. In addition, we explore new developments that promise to expand the reliability and range of clinical applications for noncontrast MRA, along with functional MRA capabilities not available with CTA or CEMRA. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:355-373.
75 citations
References
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TL;DR: Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, it is found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA.
Abstract: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.
2,831 citations
TL;DR: Stem cell migration and immune cell trafficking, as well as targeted iron oxide nanoparticles for molecular imaging studies, are at the stage of proof of concept, mainly in animal models.
1,405 citations
Journal Article•
TL;DR: The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade and can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.
Abstract: BACKGROUND AND PURPOSE: Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of conventional MR imaging in predicting glioma grade are not high. Relative cerebral blood volume (rCBV) measurements derived from perfusion MR imaging and metabolite ratios from proton MR spectroscopy are useful in predicting glioma grade. We evaluated the sensitivity, specificity, PPV, and NPV of perfusion MR imaging and MR spectroscopy compared with conventional MR imaging in grading primary gliomas. METHODS: One hundred sixty patients with a primary cerebral glioma underwent conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging, and proton MR spectroscopy. Gliomas were graded as low or high based on conventional MR imaging findings. The rCBV measurements were obtained from regions of maximum perfusion. Metabolite ratios (choline [Cho]/creatine [Cr], Cho/N-acetylaspartate [NAA], and NAA/Cr) were measured at a TE of 144 ms. Tumor grade determined with the three methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading. Sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas were also calculated. RESULTS: Sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 72.5%, 65.0%, 86.1%, and 44.1%, respectively. Statistical analysis demonstrated a threshold value of 1.75 for rCBV to provide sensitivity, specificity, PPV, and NPV of 95.0%, 57.5%, 87.0%, and 79.3%, respectively. Threshold values of 1.08 and 1.56 for Cho/Cr and 0.75 and 1.60 for Cho/NAA provided the minimum C2 and C1 errors, respectively, for determining a high-grade glioma. The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, specificity, PPV, and NPV of 93.3%, 60.0%, 87.5%, and 75.0%, respectively. Significant differences were noted in the rCBV and Cho/Cr, Cho/NAA, and NAA/Cr ratios between low- and high-grade gliomas (P CONCLUSION: The rCBV measurements and metabolite ratios both individually and in combination can increase the sensitivity and PPV when compared with conventional MR imaging alone in determining glioma grade. The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.
1,014 citations
"Current and potential imaging appli..." refers background in this paper
...rCBV (relative to a normal reference region) has been shown to correlate with survival and facilitates preoperative diagnosis by differentiating low- and highgrade tumors.(45) Moreover, elevated rCBV values can predict the transformation of low-grade gliomas into high-grade tumors 12 months before T1 enhancement appears....
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TL;DR: An ultrasmall superparamagnetic iron oxide preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals.
Abstract: An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (...
1,004 citations
TL;DR: A novel Monte Carlo model is developed with which the authors quantified the relationship between microscopic tissue parameters, NMR imaging parameters, and susceptibility contrast in vivo and demonstrated that spin echo functional images have greater microvascular sensitivity than gradient echo images, and that the specifics of the volume fraction and concentration dependence of transverse relaxivity change should allow for robust mapping of relative blood volume.
Abstract: A particularly powerful paradigm for functional MR imaging of microvascular hemodynamics incorporates paramagnetic materials that create significant image contrast. These include exogenous (lanthanide chelates) and endogenous (de-oxygenated hemoglobin) agents for mapping cerebral blood volume and neuronal activity, respectively. Accurate interpretation of these maps requires an understanding of the bio-physics of susceptibility-based image contrast. The authors developed a novel Monte Carlo model with which the authors quantified the relationship between microscopic tissue parameters, NMR imaging parameters, and susceptibility contrast in vivo. The authors found vascular permeability to water and the flow of erythrocytes to be relatively unimportant contributors to susceptibility-induced ΔR2. However, pulse sequence, echo time, and concentration of contrast agent have profound effects on the vessel size dependence of ΔR2. For a model vasculature containing both capillaries and venules, the authors predicted a linear volume fraction dependence for physiological volume changes based on recruitment and dilation, and a concentration dependence that is nonlinear and pulse sequence dependent. Using the model, the authors demonstrated that spin echo functional images have greater microvascular sensitivity than gradient echo images, and that the specifics of the volume fraction and concentration dependence of transverse relaxivity change should allow for robust mapping of relative blood volume. The authors also demonstrated excellent agreement between the predictions of their model and experimental data obtained from the serial injection of superparamagnetic contrast agent in a rat model.
961 citations