Hepatic MR imaging with ferumoxides: a multicenter clinical trial of the safety and efficacy in the detection of focal hepatic lesions.

Ros, Pablo R.; Freeny, Patrick C.; Harms, Steven E.; Seltzer, S E; Davis, Peter L.; Chan, Tao; Stillman, Arthur E.; Muroff, Lawrence R.; Runge, Val M.; Nissenbaum, Michael A.

doi:10.1148/radiology.196.2.7617864

Cited by 266 publications

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“…Ferumoxides (Feridex IV), a dextran-coated SPIO nanoparticle (hydrodynamic size: 120 -180 nm), is rapidly opsonized and endocytosed (21,39). Ferumoxides are approved by the United States Food and Drug Administration (FDA) as a MRI contrast agent.…”

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confidence: 99%

“…USPIO nanoparticles, such as the investigational agents ferumoxtran-10 and ferumoxytol, have particle diameters of 20 -50 nm and have longer plasma half-lives of 14 -30 h (21, 44). Although most commonly used for liver and lymph node imaging (5,6,9,17,25,39), USPIO agents also show excellent potential for imaging intracerebral tumors and neurological lesions in the central nervous system (CNS) (19,30,41). Ferumoxides have not been effective for CNS imaging (19,30,41).…”

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In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

Wu¹,

Muldoon²,

Várallyay³

et al. 2007

American Journal of Physiology-Cell Physiology

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Wu YJ, Muldoon LL, Varallyay C, Markwardt S, Jones RE, Neuwelt EA. In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging. Am J Physiol Cell Physiol 293: C1698-C1708, 2007. First published September 26, 2007; doi:10.1152/ajpcell.00215.2007.-Cellular labeling with ferumoxides (Feridex IV) superparamagnetic iron oxide nanoparticles can be used to monitor cells in vivo by MRI. The objective of this study was to use histology and MRI to evaluate an in vivo, as opposed to in vitro, technique for labeling of mononuclear leukocytes as a means of tracking inflammatory processes in the brain. Long-Evans rats were intravenously injected with 20 mg/kg ferumoxides, ferumoxtran-10, or ferumoxytol with or without protamine sulfate. Leukocytes and splenocytes were evaluated by cell sorting and iron histochemistry or were implanted into the brain for MRI. Injection of ferumoxides/ protamine sulfate complex IV resulted in iron labeling of leukocytes (ranging from 7.4 Ϯ 0.5% to 12.5 Ϯ 0.9% with average 9.2 Ϯ 0.8%) compared with ferumoxides (ranging from 3.9 Ϯ 0.4% to 6.3 Ϯ 0.5% with average 5.0 Ϯ 0.5%) or protamine sulfate alone (ranging from 0% to 0.9 Ϯ 0.7% with average 0.3 Ϯ 0.3%). Cell sorting analysis indicated that iron-labeled cells were enriched for cell types positive for the myelomonocytic marker (CD11b/c) and the B lymphocyte marker (CD45RA) and depleted in the T cell marker (CD3). Neither ferumoxtran-10 nor ferumoxytol with protamine sulfate labeled leukocytes. In vivo ferumoxides/protamine sulfate-loaded leukocytes and splenocytes were detected by MRI after intracerebral injection. Ferumoxides/protamine complex labeled CD45RA-positive and CD11b/c-positive leukocytes in vivo without immediate toxicity. The dose of feumoxides in this report is much higher than the approved human dose, so additional animal studies are required before this approach could be translated to the clinic. These results might provide useful information for monitoring leukocyte trafficking into the brain. leukocyte trafficking; brain; B lymphocyte; rat SUPERPARAMAGNETIC IRON OXIDE (SPIO) and ultra-small SPIO (USPIO) nanoparticle agents, consisting of an iron oxide core with a variable carbohydrate coating, are gaining use for MRI.

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In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

Wu¹,

Muldoon²,

Várallyay³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…Higher accuracy in liver cancer detection potentially changes the clinical treatment of patients with liver cancer. The report of Ros et al states that the proportionate change in clinical treatment was as high as 59% after examination using SPIO-enhanced MR [21] . For detection of lesions larger than 1 cm, there was no significant difference among the findings of the different sequences (excluding pre- Ferucarbotran is an SPIO agent that can be injected as a bolus [10] .…”

Section: Discussionmentioning

confidence: 99%

FerucarbotranversusGd-DTPA-enhanced MR imaging in the detection of focal hepatic lesions

Cheng

Zeng²,

Yan³

et al. 2007

WJG

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“…To date, iron oxide nanoparticles are the most advanced, as some particles are already approved for applications other than brain imaging. SPIO, such as ferumoxides (Endorem®, Guerbet in Europe and Feridex®, AMAG Pharmaceuticals Inc. in the USA and Japan), are approved by the United States Food and Drug Administration for MR imaging of liver tumors [125] and USPIO ferumoxytol (Feraheme, AMAG Pharmaceutical Inc.) is also Food and Drug Administration-approved for iron replacement therapy in patients with chronic renal failure. Another USPIO, ferumoxtran-10 (Sinerem, Guerbet, Europe, also known as Combidex, AMAG Pharmaceuticals Inc., USA and Japan), is still investigational, although it has completed phase III trials [126] and its safety profile assessed from pooled clinical studies in 1777 adults did not show major adverse effects [127].…”

Section: Translation To Clinical Usementioning

confidence: 99%

Neuroinflammatory Imaging Biomarkers: Relevance to Multiple Sclerosis and its Therapy

Tourdias

Dousset

2013

Neurotherapeutics

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Magnetic resonance imaging is an established tool in the management of multiple sclerosis (MS). Loss of blood brain barrier integrity assessed by gadolinium (Gd) enhancement is the current standard marker of MS activity. To explore the complex cascade of the inflammatory events, other magnetic resonance imaging, but also positron emission tomographic markers reviewed in this article are being developed to address active neuroinflammation with increased sensitivity and specificity. Alternative magnetic resonance contrast agents, positron emission tomographic tracers and imaging techniques could be more sensitive than Gd to early blood brain barrier alteration, and they could assess the inflammatory cell recruitment and/or the associated edema accumulation. These markers of active neuroinflammation, although some of them are limited to experimental studies, could find great relevance to complete Gd information and thereby increase our understanding of acute lesion pathophysiology and its noninvasive follow-up, especially to monitor treatment efficacy. Furthermore, such accurate markers of inflammation combined with those of neurodegeneration hold promise to provide a more complete picture of MS, which will be of great benefit for future therapeutic strategies. [4]. Currently, a large battery of MRI methods is being developed (measurement of atrophy, T1 hypointensity, iron mapping, spectroscopy, diffusion tensor, magnetization transfer ratio, imaging of cortical anomalies, and so forth) to provide quantitative information on the severity of the neurodegenerative component of MS [5] that is thought to be an important substrate of long-term irreversible disability. By contrast, gadolinium (Gd) enhancement of lesions is the only reference method to assess blood brain barrier (BBB) permeability that reflects the inflammatory component of MS [6], and which is the predominant pathogenic mechanism in the early stages of approximately 85% of patients with a relapsing remitting form of MS. Although Gd is a powerful marker, limiting active inflammation to Gdenhanced lesions is an oversimplification, as Gd can lack sensitivity, specificity, and does not address the cellular and edematous components that accompany active neuroinflammation [7] (Fig. 1). Furthermore, Gd cannot address subtle, but disseminated, inflammation that contributes to clinical progression together with neurodegenerative axonal loss. Consequently, other markers of active neuroinflammation are being developed in experimental animal models, and some have already been translated to human studies. These new markers of active inflammation aim to reflect the BBB permeability more accurately than Gd and to assess the Electronic supplementary material The online version of this article

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Hepatic MR imaging with ferumoxides: a multicenter clinical trial of the safety and efficacy in the detection of focal hepatic lesions.

Abstract: Ferumoxides is a safe and efficacious contrast agent for the detection of focal liver lesions on T2-weighted images.

Cited by 266 publications

References 0 publications

In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

FerucarbotranversusGd-DTPA-enhanced MR imaging in the detection of focal hepatic lesions

Neuroinflammatory Imaging Biomarkers: Relevance to Multiple Sclerosis and its Therapy

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