Parenteral ferumoxytol interaction with magnetic resonance imaging: a case report, review of the literature and advisory warning
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Ferumoxytol is a safe and effective parenteral therapy used for the treatment of iron deficiency anaemia that has recently been approved for use in North America and in Europe.
Ferumoxytol consists of a superparamagnetic iron oxide (SPIO) core, which causes T1, T2 and T2* shortening effects, and a carbohydrate shell, which results in a prolonged intravascular half life.
These properties are under-reported and not well recognised. They can interfere with MRI interpretation, potentially masking enhancement and rendering examinations non-diagnostic or simulating pathologic disease states. Both radiologists and non-radiologist physicians must consider the potential interaction of ferumoxytol with MRI when interpreting and prescribing MRI examinations in their patients.
• Ferumoxytol has recently been approved for the treatment of iron deficiency anaemia.
• Ferumoxytol is a small iron oxide particle with prolonged intravascular half life and T1, T2 and T2* shortening effects.
• Administration of ferumoxytol can mask enhancement, rendering MRI studies potentially non-diagnostic.
• Ferumoxytol can mimic diseases such as haemosiderosis, haemochromatosis and superficial siderosis.
• Ferumoxytol interactions with MRI must be recognised by radiologists and non-radiologist physicians.
KeywordsFerumoxytol Gadolinium Magnetic resonance imaging Small iron oxide particle Iron
Super-paramagnetic iron oxide particle
Reticulo-endothelial cell system
Gradient recalled echo
Fast spin echo
Ferumoxytol (marketed in Europe as Rienso and North America as Feraheme by Takeda Inc. and AMAG Pharmaceuticals) has recently been approved in Europe and North America for the parenteral treatment of iron deficiency anaemia in patients with chronic kidney disease [1, 2, 3].
Parenteral iron therapy can be used safely to treat iron deficiency anaemia in patients with chronic kidney disease and other chronic diseases and represents an attractive alternative to oral iron therapy with more effective results based on a recent systematic review . Feraheme or Rienso (30 mg/ml, ferumoxytol) is to be administered as an undiluted intravenous (IV) injection delivered at a rate of up to 1 ml/s (30 mg/s) for a total dose of 510 mg IV followed by a second 510-mg IV injection 2 to 8 days later . Improved outcomes when compared to oral therapy  and intravenous bolus injection compared to other parenteral iron suspensions that require longer infusions will likely lead to increased use of ferumoxytol in clinical practice .
Ferumoxytol is a haematinic agent that consists of an ultrasmall superparamagnetic iron oxide (SPIO) core coated with a carbohydrate shell to help isolate the bioactive iron from plasma elements until it is taken up by the reticuloendothelial system (RES) macrophages of the liver, spleen and bone marrow . Ferumoxytol, similar to other SPIO agents, results in T1, T2 and T2* shortening effects with MRI, which can impact image interpretation and clinical practice . The pharmaceutical composition of ferumoxytol (SPIO encased in carbohydrate shell) results in a prolonged circulating half-life (14–15 h) in the intravascular space (blood pool), which can alter the relaxivity characteristics of the blood pool for days to months . The T1 shortening effects and extremely long intravascular half-life of ferumoxytol render it particularly problematic with the use of traditional gadolinium-enhanced GRE pulse sequences. Extracellular gadolinium agents also rely on T1 shortening effects, which can be masked after patients have received ferumoxytol, potentially rendering examinations non-diagnostic. This effect has been recently reported  and occurred in our case. This effect could have further implications in other areas of MRI requiring the use of gadolinium for diagnosis including breast and cardiac imaging. Furthermore, failure to appreciate that ferumoxytol has been administered could result in the erroneous diagnosis of iron overload (haemosiderosis or haemochromatosis) in the abdomen. In our patient, superficial siderosis in the brain could have been erroneously diagnosed on GRE images of the brain presumably related to ferumoxytol accumulation in the leptomeninges. A key to diagnosis if the history of the ferumoxytol injection is not known or not provided is findings of enhancement of the blood pool on pre-contrast GRE sequences. Low signal intensity of lymph nodes on both T1 GRE and T2 pulse sequences is also an indicator that the patient may have received ferumoxytol, although this could also be seen with calcification.
The T1 shortening properties and prolonged intravascular half-life of ferumoxytol could represent an alternative to enhanced MRI in patients with compromised renal function who are at risk for nephrogenic systemic fibrosis when using traditional gadolinium contrast agents that are cleared by the kidneys . Ferumoxytol, like other SPIO agents, is not cleared by glomerular filtration but by macrophages in the RES, and this feature could also serve to help detect pathology in the RES where normal uptake is not observed, such as in the diagnosis of metastatic lymphadenopathy .
The ferumoxytol package insert warns of potential MRI effects lasting for up to 3 months . A recent prospective study that monitored iron clearance from the liver in patients receiving ferumoxytol showed a wide variability in iron clearance times ranging from 3 months to 11 months, with several participants showing persistent T2 shortening effects after 11 months .
Based on our local experience and the limited information available in the literature, our institution has developed guidelines for radiologists and non-radiologist physicians to consider when ordering, prescribing or interpreting MRI studies in patients receiving ferumoxytol. For patients who require MRI with anticipated treatment with ferumoxytol, it is suggested that the patient undergo MRI prior to initiation of therapy. For patients who have recently received the medication and require gadolinium-enhanced MRI, it is suggested that the exam be deferred for 3 months or that another imaging modality (such as computed tomography) be considered as an alternative where appropriate. For patients who have recently received ferumoxytol and require MRI without gadolinium, each case should be considered individually with anticipated problems likely occurring mostly in those pathologies that involve organs of the RES.
The potential interaction of ferumoxytol with clinical MRI studies can impact interpretation and is important for both radiologists and non-radiologist physicians to appreciate when requesting and interpreting MRI examinations for their patients. The recent administration of ferumoxytol can mask enhancement and render MRI examinations non-diagnostic. Furthermore, ferumoxytol can mimic disease states such as haemosiderosis or superficial siderosis. This interaction is under-reported and poorly understood by radiologists and the medical community at large. Increased use of ferumoxytol in patients with chronic illness and iron deficiency is expected and will result in a greater occurrence of potential interactions with MRIs.
Conflict of interest
The authors declare no conflicts of interest. No funding was received for this work.
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