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

BACKGROUND AND PURPOSE: Patients with suspected brain tumors typically undergo 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 pre-contrast imaging for structural delineation of intra-axial malignant brain lesions. MATERIALS AND METHODS: This was a prospective, blinded re-read study of MRI 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 pre-contrast images in separate reading sessions organized by an independent contract research organization. The 3 primary endpoints were the degree of contrast enhancement, border delineation, and the internal morphology of lesions, assessed using a 4-point visualization scale (1=none/poor; 4=excellent). RESULTS: In total, 153 patients were enrolled in the study (median age, 54 years; 57% male; 92% white). All 3 readers scored ferumoxytol-enhanced MRI images significantly higher than the pre-contrast images for visualizing lesions (p<0.001 for each primary endpoint). Average mean scores across readers for ferumoxytol-enhanced images were 2.8 for contrast enhancement, 3.0 for border delineation, and 2.6 for internal morphology, compared to 1.0, 2.1, and 1.7, respectively, for the pre-contrast images (p<0.001 for all). Safety data indicated that ferumoxytol administration was well-tolerated with adverse events consistent with its profile as an iron replacement therapy. CONCLUSIONS: This study provides robust evidence that ferumoxytol-enhanced MRI improves lesion visualization compared to pre-contrast 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.