Superiority of Ferumoxytol MRI over Precontrast Imaging in Patients with Malignant Brain Lesions

Patients with suspected brain tumors typically undergo an MRI with an IV contrast agent to detect regions of disrupted BBB caused by the tumor. Gadolinium-based contrast agents are standard for enhancing lesion visualization but may be contraindicated in patients with renal insufficiency. Ferumoxytol is an iron oxide nanoparticle approved for the treatment of iron deficiency anemia, and unlike gadolinium-based contrast agents, is not contraindicated in patients with renal impairment. Our study aimed to evaluate whether ferumoxytol-enhanced MRI is superior to precontrast imaging for structural delineation of intra-axial malignant brain lesions.

This was a prospective, blinded reread study of MR images from patients with known or suspected intra-axial primary malignant or metastatic brain tumors, enrolled in an Institutional Review Board-approved research study, to support an FDA New Drug Application. Following FDA guidance, 3 independent neuroradiologist readers, blinded to contrast agent information, evaluated brain lesions of randomly ordered ferumoxytol-enhanced, gadolinium-enhanced, or precontrast images in separate reading sessions organized by an independent contract research organization. The 3 primary end points were the degree of contrast enhancement (CE), border delineation (BD), and the internal morphology (IM) of lesions, assessed using a 4-point visualization scale (1 = none/poor; 4 = excellent).

In total, 153 patients were enrolled in the study (median age, 54 years; 57% men; 92% white). All 3 readers scored ferumoxytol-enhanced MR images significantly higher than the precontrast images for visualizing lesions (P < .001 for each primary end point). Average mean scores across readers for ferumoxytol-enhanced images were 2.8 for CE, 3.0 for BD, and 2.6 for IM, compared with 1.0, 2.1, and 1.7, respectively, for the precontrast images (P < .001 for all). Safety data indicated that ferumoxytol administration was well-tolerated with adverse events consistent with its profile as an iron-replacement therapy.

This study provides robust evidence that ferumoxytol-enhanced MRI improves lesion visualization compared with precontrast imaging. Ferumoxytol, as an MRI contrast agent in brain tumor imaging, may provide a valuable clinical alternative to gadolinium-based contrast agents in appropriate patient groups.