Clinical Applications of Iron Oxide Nanoparticles for Magnetic Resonance Imaging of Brain Tumors

Michael, Cassia; Telischak, N; Feng, Dan; Holdsworth, Samantha J.; Yeom, Kristen W.; Daldrup-Link, Heike E.

doi:10.2217/nnm.14.203

Cited by 105 publications

(62 citation statements)

References 135 publications

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“…MRI uses a combination of magnetic field radiofrequency pulse to image body organs containing IONP. They improve contrast of image and ensure imaging of target organs with particular safety for pediatrics and geriatrics patients (134)(135)(136)(137)(138).…”

Section: Iron Nanoparticlesmentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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-Nanotechnology has opened a new horizon of research in various fields including applied physics, chemistry, electronics, optics, robotics, biotechnology and medicine. In the biomedical field, nanomaterials have shown remarkable potential as theranostic agents. Materials which are considered inert are often used in nanomedicine owning to their nontoxic profile. At nanoscale, these inert materials have shown unique properties that differ from bulk and dissolved counterparts. In the case of metals, this unique behavior not only imparts paramount advantages but also confers toxicity due to their unwanted interaction with different cellular processes. In the literature, the toxicity of nanoparticles made from inert materials has been investigated and many of these have revealed toxic potential under specific conditions. The surge to understand underlying mechanism of toxicity has increased and different means have been employed to overcome toxicity problems associated with these agents. In this review, we have focused nanoparticles of three inert metallic materials i.e. gold, silver and iron as these are regarded as biologically inert in the bulk and dissolved form. These materials have gained wider research interest and studies indicating the toxicity of these materials are also emerging. Oxidative stress, physical binding and interference with intracellular signaling are the major role player in nanotoxicity and their predominance is highly dependent upon size, surface coating and administered dose of nanoparticles. Current strategies to overcome toxicity have also been reviewed in the light of recent literature. The authors also suggested that uniform testing standards and well-designed studies are needed to evaluate nanotoxicity of these materials that are otherwise considered as inert.

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Section: Iron Nanoparticlesmentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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“…Because neuroinflammation results in tissue changes that occur before loss of function, in vivo imaging of inflammation is of significant clinical interest. Such imaging is enabled by ferumoxytol, a viral-sized (17-31 nm) ultrasmall superparagmagnetic iron oxide (USPIO) nanoparticle 1, 2 . Ferumoxytol is approved by the Federal Drug Administration for treatment of iron deficiency anemia in patients with chronic kidney disease, but can be used off-label as a MRI contrast agent to detect CNS lesions and vascular abnormalities in brain 2-4 .…”

Section: Introductionmentioning

confidence: 99%

“…Such imaging is enabled by ferumoxytol, a viral-sized (17-31 nm) ultrasmall superparagmagnetic iron oxide (USPIO) nanoparticle 1, 2 . Ferumoxytol is approved by the Federal Drug Administration for treatment of iron deficiency anemia in patients with chronic kidney disease, but can be used off-label as a MRI contrast agent to detect CNS lesions and vascular abnormalities in brain 2-4 . While conventional gadolinium-based contrast agents allow rapid, transient, non-specific imaging of blood-brain barrier (BBB) permeability, they cannot differentiate neuroinflammation due to trauma from that due to tumor, for example 5 .…”

Section: Introductionmentioning

confidence: 99%

“…The USPIO nanoparticle ferumoxytol is an emerging alternative approach for contrast enhancement in neuroimaging because, during neuroinflammation, it traffics from systemic circulation to reactive lesions and increases the contrast between affected and normal tissues 1 . Ongoing phase II clinical trials using ferumoxytol in patients with high-grade gliomas and multiple sclerosis plaques show that ferumoxytol-contrasted MRI may resolve phenomena including vascular changes, altered BBB permeability, long-term tissue changes in tumors, brain parenchyma, and neurological lesions on MRI (clinicaltrials.gov NCT00660543) 2, 6-8 . Despite these clinical advances, the timing and mechanisms of ferumoxytol trafficking into the brain, uptake into neuroinflammatory lesions, and cell-type specificity are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific

McConnell

Schwartz

Richardson

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo. We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+/CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.

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“…Compared to GBCA, it may not require leakage correction or preload dosing [3]. Perfusion MRI has been used clinically as a biomarker to prospectively differentiate pseudoprogression from disease progression [4–7], and relative cerebral blood volume (rCBV) measurements using ferumoxytol as an MRI contrast agent can discriminate true progression from pseudoprogression in GBM using a mean rCBV threshold of 1.75 [3, 8]. The use of small paramagnetic iron oxides (SPIOs), such as ferumoxytol, was first published as an MR-based imaging agent for cancer in 1989, and has increased exponentially in the last decade.…”

Section: Introductionmentioning

confidence: 99%

Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab

Netto

Schwartz

Várallyay

et al. 2016

Fluids Barriers CNS

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BackgroundNeovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management.Methods16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV “hot spot” (mean of the highest rCBV in a 1.08 cm2 area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion.ResultsGBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis.ConclusionsDecreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.

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Clinical Applications of Iron Oxide Nanoparticles for Magnetic Resonance Imaging of Brain Tumors

Cited by 105 publications

References 135 publications

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific

Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab

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