Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)?
Edward A Neuwelt, Bronwyn E Hamilton, Csanad G Varallyay, William R Rooney, Robert D Edelman, Paula M Jacobs, Suzanne G Watnick, Edward A Neuwelt, Bronwyn E Hamilton, Csanad G Varallyay, William R Rooney, Robert D Edelman, Paula M Jacobs, Suzanne G Watnick
Abstract
Gadolinium (Gd) based contrast agents (GBCAs) in magnetic resonance imaging (MRI) are used in daily clinical practice and appear safe in most patients; however, nephrogenic systemic fibrosis (NSF) is a recently recognized severe complication associated with GBCAs. It affects primarily patients with renal disease, such as stage 4 or 5 chronic kidney disease (CKD; glomerular filtration rate <30 ml/min per 1.73 m(2)), acute kidney injury, or kidney and liver transplant recipients with kidney dysfunction. Contrast-enhanced MRI and computed tomography (CT) scans provide important clinical information and influence patient management. An alternative contrast agent is needed to obtain adequate imaging results while avoiding the risk of NSF in this vulnerable patient group. One potential alternative is ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, which provide enhancement characteristics similar to GBCAs. We review our experience in approximately 150 patients on the potential benefits of the USPIOs ferumoxtran-10 and ferumoxytol. We focus on central nervous system (CNS) MRI but also review imaging of other vascular beds. Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney function does not alter the safety profile. We conclude that for both CNS MR imaging and MR angiography, USPIO agents like ferumoxytol are a viable option for patients at risk for NSF.
Figures
References
- Varallyay P, Nesbit G, Muldoon LL, et al. Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors. AJNR Am J Neuroradiol. 2002;23:510–519.
- Manninger SP, Muldoon LL, Nesbit G, et al. An exploratory study of ferumoxtran-10 nanoparticles as a blood-brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions. AJNR Am J Neuroradiol. 2005;26:2290–2300.
- Neuwelt EA, Varallyay CG, Manninger S, et al. The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study. Neurosurgery. 2007;60:601–611. discussion 611–602.
- Tombach B, Reimer P, Bremer C, et al. First-pass and equilibrium-MRA of the aortoiliac region with a superparamagnetic iron oxide blood pool MR contrast agent (SH U 555 C): results of a human pilot study. NMR Biomed. 2004;17:500–506.
- Metz S, Bonaterra G, Rudelius M, et al. Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol. 2004;14:1851–1858.
- Vellinga MM, Oude Engberink RD, Seewann A, et al. Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement. Brain. 2008;131:800–807.
- Wu YJ, Muldoon LL, Varallyay C, et al. In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging. Am J Physiol Cell Physiol. 2007;293:C1698–C1708.
- Neuwelt EA, Varallyay P, Bago AG, et al. Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours. Neuropathol Appl Neurobiol. 2004;30:456–471.
- Jung CW, Jacobs P. Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging. 1995;13:661–674.
- Jacobs P, Shenouda M. A phase I pharmacokinetics and safety study of ferumoxytol, a new blood pool and macrophage specific superparamagnetic iron oxide MR contrast agent.. RSNA Scientific Assembly and Annual Meeting Program. Meeting Proceedings; Oak Brook: Illinois. 2003.
- Landry R, Jacobs PM, Davis R, et al. Pharmacokinetic study of ferumoxytol: a new iron replacement therapy in normal subjects and hemodialysis patients. Am J Nephrol. 2005;25:400–410.
- Neuwelt EA, Weissleder R, Nilaver G, et al. Delivery of virus-sized iron oxide particles to rodent CNS neurons. Neurosurgery. 1994;34:777–784.
- Murillo T, Sandquist C, Jacobs PM, et al. Imaging brain tumors with ferumoxtran-10, a nanoparticle magnetic resonance contrast agent. Therapy. 2005;2:871–882.
- Swaminathan S, Shah SV. New insights into nephrogenic systemic fibrosis. J Am Soc Nephrol. 2007;18:2636–2643.
- Willicombe M, Cunningham J. Nephrogenic systemic fibrosis: a sufficient reason to avoid gadolinium-based contrast in all patients with renal impairment? Semin Dial. 2008;21:140–141.
- Swaminathan S, Horn TD, Pellowski D, et al. Nephrogenic systemic fibrosis, gadolinium, and iron mobilization. N Engl J Med. 2007;357:720–722.
- Besarab A, Coyne D, Bolton WK, et al. Ferumoxytol as an intravenous iron replacement therapy: safety results from two phase III studies in subject with chronic kidney diseases (CKD).. American Society of Nephrology 40th Annual Meeting and Scientific Exposition.; San Francisco. 2007.p. SU-PO805.
- Bongartz G. Imaging in the time of NFD/NSF: do we have to change our routines concerning renal insufficiency? MAGMA. 2007;20:57–62.
- Caravan P, Ellison JJ, McMurry TJ, et al. Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev. 1999;99:2293–2352.
- Grobner T, Prischl FC. Gadolinium and nephrogenic systemic fibrosis. Kidney Int. 2007;72:260–264.
- Hunt MA, Bago AG, Neuwelt EA. Single-dose contrast agent for intraoperative MR imaging of intrinsic brain tumors by using ferumoxtran-10. AJNR Am J Neuroradiol. 2005;26:1084–1088.
- Abraham JL, Thakral C. Tissue distribution and kinetics of gadolinium and nephrogenic systemic fibrosis. Eur J Radiol. 2008;66:200–207.
- Ersoy H, Jacobs P, Kent CK, et al. Blood pool MR angiography of aortic stent-graft endoleak. AJR Am J Roentgenol. 2004;182:1181–1186.
- Bremerich J, Bilecen D, Reimer P. MR angiography with blood pool contrast agents. Eur Radiol. 2007;17:3017–3024.
- Corot C, Petry KG, Trivedi R, et al. Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging. Invest Radiol. 2004;39:619–625.
- Akella NS, Twieg DB, Mikkelsen T, et al. Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic resonance imaging: quality and analysis results of a phase I trial. J Magn Reson Imaging. 2004;20:913–922.
- Li W, Tutton S, Vu AT, et al. First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Reson Imaging. 2005;21:46–52.
Source: PubMed