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American Journal of Hematology Jan 2016It is estimated that one-third of the world's population is anemic, the majority being due to iron deficiency (ID). In adults, ID is associated with fatigue in the... (Review)
Review
It is estimated that one-third of the world's population is anemic, the majority being due to iron deficiency (ID). In adults, ID is associated with fatigue in the absence of anemia, restless legs syndrome, pica and, in neonates, delayed growth and development. In adolescents, ID is associated with decrements in learning and behavioral abnormalities. In the absence of a clear cause, search for a source of bleeding is indicated. No single test is diagnostic of ID unless the serum ferritin is low or the percent transferrin saturation is low with an elevated total iron binding capacity. Oral iron is considered front line therapy except for conditions such as gastric bypass, heavy uterine bleeding, inflammatory bowel disease, and hereditary hemorrhagic telangiectasia. Oral iron has many unpleasant side effects, resulting in low patient adherence. For patients intolerant of, or unresponsive to, oral iron, intravenous (IV) administration is the preferred route. While early formulations were associated with a high incidence of serious adverse events (SAEs), newer formulations are much safer with SAEs occurring very infrequently. Full replacement doses can be administered in a matter of minutes to a few hours. Nevertheless, there remains a reluctance to use IV iron due to a misunderstanding of the safety of the available formulations. IV iron is safe and effective in all clinical circumstances including pregnancy. The preponderance of published evidence suggests IV iron therapy is underutilized and we believe that IV iron should be moved forward in the treatment of ID and iron deficiency anemia (IDA).
Topics: Administration, Oral; Anemia, Iron-Deficiency; Ferritins; Ferrosoferric Oxide; Ferrous Compounds; Hematinics; Humans; Injections, Intravenous; Iron-Dextran Complex
PubMed: 26408108
DOI: 10.1002/ajh.24201 -
Nature Nanotechnology Nov 2016Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as...
Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Polarity; Female; Ferrosoferric Oxide; Humans; Inflammation; Liver Neoplasms; Lung Neoplasms; Macrophages; Mammary Neoplasms, Experimental; Metal Nanoparticles; Mice, Inbred NOD; Mice, Inbred Strains; Xenograft Model Antitumor Assays
PubMed: 27668795
DOI: 10.1038/nnano.2016.168 -
Theranostics 2022Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients... (Review)
Review
Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease. In recent years, ferumoxytol has also been demonstrated to have potential for many additional biomedical applications due to its excellent inherent physical properties, such as superparamagnetism, biocatalytic activity, and immunomodulatory behavior. With good safety and clearance profiles, ferumoxytol has been extensively utilized in both preclinical and clinical studies. Here, we first introduce the medical needs and the value of current iron oxide nanoparticle formulations in the market. We then focus on ferumoxytol nanoparticles and their physicochemical, diagnostic, and therapeutic properties. We include examples describing their use in various biomedical applications, including magnetic resonance imaging (MRI), multimodality imaging, iron deficiency treatment, immunotherapy, microbial biofilm treatment and drug delivery. Finally, we provide a brief conclusion and offer our perspectives on the current limitations and emerging applications of ferumoxytol in biomedicine. Overall, this review provides a comprehensive summary of the developments of ferumoxytol as an agent with diagnostic, therapeutic, and theranostic functionalities.
Topics: Animals; Antineoplastic Agents; Drug Approval; Drug Repositioning; Ferrosoferric Oxide; Humans; Iron; Iron Deficiencies; Magnetic Resonance Imaging; Metal Nanoparticles; Precision Medicine; United States; United States Food and Drug Administration
PubMed: 34976214
DOI: 10.7150/thno.67375 -
Clinical Radiology Aug 2016The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated... (Review)
Review
The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated nephrogenic systemic fibrosis in those with severely impaired renal function spurred developments in low-dose CEMRA and non-contrast MRA as well as efforts to seek alternative MR contrast agents. Originally developed for MR imaging use, ferumoxytol (an ultra-small superparamagnetic iron oxide nanoparticle), is currently approved by the US Food and Drug Administration for the treatment of iron deficiency anaemia in adults with renal disease. Since its clinical availability in 2009, there has been rising interest in the scientific and clinical use of ferumoxytol as an MR contrast agent. The unique physicochemical and pharmacokinetic properties of ferumoxytol, including its long intravascular half-life and high r1 relaxivity, support a spectrum of MRI applications beyond the scope of Gd-based contrast agents. Moreover, whereas Gd is not found in biological systems, iron is essential for normal metabolism, and nutritional iron deficiency poses major public health challenges worldwide. Once the carbohydrate shell of ferumoxytol is degraded, the elemental iron at its core is incorporated into the reticuloendothelial system. These considerations position ferumoxytol as a potential game changer in the field of CEMRA and MRI. In this paper, we aim to summarise our experience with the cardiovascular applications of ferumoxytol and provide a brief synopsis of ongoing investigations on ferumoxytol-enhanced MR applications.
Topics: Cardiovascular Diseases; Contrast Media; Ferrosoferric Oxide; Humans; Image Enhancement; Magnetic Resonance Angiography; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution
PubMed: 27221526
DOI: 10.1016/j.crad.2016.03.020 -
Clinical Radiology Jan 2019Ferumoxytol is a promising non-gadolinium-based contrast agent with numerous varied magnetic resonance imaging applications. Previous reviews of vascular applications... (Review)
Review
Ferumoxytol is a promising non-gadolinium-based contrast agent with numerous varied magnetic resonance imaging applications. Previous reviews of vascular applications have focused primarily on cardiac and aortic applications. After considering safety concerns and technical issues, the objective of this paper is to explore peripheral applications for ferumoxytol-enhanced magnetic resonance angiography (MRA) and venography (MRV) in the upper and lower extremities. Separate searches for each of the following keywords were performed in pubmed: "ferumoxytol," "ultrasmall superparamagnetic iron oxide," and "USPIO." All studies pertaining to MRA or MRV in humans are included in this review. Case-based examples of various peripheral applications are used to supplement a relatively scant literature in this space. Ferumoxytol's unique properties including high T1 relaxivity and prolonged intravascular half-life make it the optimal vascular imaging contrast agent on the market and one whose vast potential has only begun to be tapped.
Topics: Blood Vessels; Contrast Media; Ferrosoferric Oxide; Humans; Magnetic Resonance Angiography; Peripheral Vascular Diseases; Transcatheter Aortic Valve Replacement
PubMed: 29731126
DOI: 10.1016/j.crad.2018.02.021 -
FEBS Letters Apr 2013Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both... (Review)
Review
Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications.
Topics: Contrast Media; Ferrosoferric Oxide; Image Enhancement; Magnetic Resonance Imaging; Metalloproteins; Models, Chemical; Models, Molecular; Mutation; Protein Engineering
PubMed: 23376346
DOI: 10.1016/j.febslet.2013.01.044 -
Kidney International Jul 2017Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG... (Review)
Review
Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. 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. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.
Topics: Adolescent; Adult; Animals; Atlases as Topic; Child, Preschool; Contrast Media; Female; Ferrosoferric Oxide; Hematinics; Humans; Kidney; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; Renal Elimination; Renal Insufficiency, Chronic; Reproducibility of Results
PubMed: 28434822
DOI: 10.1016/j.kint.2016.12.037 -
Wiley Interdisciplinary Reviews.... Jul 2019"Off the shelf" allogeneic stem cell transplants and stem cell nano-composites are being used for the treatment of degenerative bone diseases. However, major and minor... (Review)
Review
"Off the shelf" allogeneic stem cell transplants and stem cell nano-composites are being used for the treatment of degenerative bone diseases. However, major and minor histocompatibility antigens of therapeutic cell transplants can be recognized as foreign and lead to their rejection by the host immune system. If a host immune response is identified within the first week post-transplant, immune modulating therapies could be applied to prevent graft failure and support engraftment. Ferumoxytol (Feraheme™) is an FDA approved iron oxide nanoparticle preparation for the treatment of anemia in patients. Ferumoxytol can be used "off label" as an magnetic resonance (MR) contrast agent, as these nanoparticles provide measurable signal changes on magnetic resonance imaging (MRI). In this focused review article, we will discuss three methods to localize and identify innate immune responses to stem cell transplants using ferumoxytol-enhanced MRI, which are based on tracking stem cells, tracking macrophages or detecting mediators of cell death: (a) monitor MRI signal changes of ferumoxytol-labeled stem cells in the presence or absence of innate immune responses, (b) monitor influx of ferumoxytol-labeled macrophages into stem cell implants, and (c) monitor apoptosis of stem cell implants with caspase-3 activatable nanoparticles. These techniques can detect transplant failure at an early stage, when immune-modulating interventions can potentially preserve the viability of the cell transplants and thereby improve bone and cartilage repair outcomes. Approaches 1 and 2 are immediately translatable to clinical practice. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Diagnostic Tools > Biosensing.
Topics: Contrast Media; Ferrosoferric Oxide; Humans; Macrophages; Magnetic Resonance Imaging; Magnetite Nanoparticles; Molecular Imaging; Stem Cell Transplantation; Stem Cells
PubMed: 30734542
DOI: 10.1002/wnan.1552 -
Current Biology : CB May 2010Few subjects in animal behavior have more exotic mystery than magnetic-field sensitivity. A force we cannot sense, generated by events no one completely understands,...
Few subjects in animal behavior have more exotic mystery than magnetic-field sensitivity. A force we cannot sense, generated by events no one completely understands, creates field lines that pass through our bodies without any evident effect on us or on them. It is an energy felt as much by migrating lobsters on the sea floor as by ocean-crossing birds thousands of meters overhead, transduced in generally poorly understood ways. Despite the blindness of humans, modern life depends on this invisible, ghostlike field. Aside from lights and heaters, nearly every electrical device we own makes use of electromagnetism, and that same magnetism is essential in generating the power these new-found necessities consume. But for many animals, the reliance is far older and more basic: their life-or-death ability to find their way around in the world depends on correctly interpreting the earth's magnetic field.
Topics: Animals; Electromagnetic Phenomena; Ferrosoferric Oxide; Perception; Sensation
PubMed: 20504748
DOI: 10.1016/j.cub.2010.03.045 -
Microbiological Research Oct 2017Bacterial magnetosome, synthetized by magnetosome-producing microorganisms including magnetotactic bacteria (MTB) and some non-magnetotactic bacteria (Non-MTB), is a new... (Review)
Review
Bacterial magnetosome, synthetized by magnetosome-producing microorganisms including magnetotactic bacteria (MTB) and some non-magnetotactic bacteria (Non-MTB), is a new type of material comprising magnetic nanocrystals surrounded by a phospholipid bilayer. Because of the special properties such as single magnetic domain, excellent biocompatibility and surface modification, bacterial magnetosome has become an increasingly attractive for researchers in biology, medicine, paleomagnetism, geology and environmental science. This review briefly describes the general feature of magnetosome-producing microorganisms. This article also highlights recent advances in the understanding of the biochemical and magnetic characteristics of bacterial magnetosome, as well as the magnetosome formation mechanism including iron ions uptake, magnetosome membrane formation, biomineralization and magnetosome chain assembly. Finally, this review presents the potential applications of bacterial magnetosome in biomedicine, wastewater treatment, and the significance of mineralization of magnetosome in biology and geology.
Topics: Cell Membrane; Ferrosoferric Oxide; Iron; Magnetic Fields; Magnetosomes; Magnetospirillum; Sulfides
PubMed: 28754204
DOI: 10.1016/j.micres.2017.06.005