Iron-Oxide Nanoparticles as Magnetic Resonance Contrast Agents: Expanding Their Potential Beyond Iron Replacement Therapy.

Abstract 1998

Poster Board I-1020

Ferumoxytol (Feraheme™), an iron oxide nanoparticle, was approved as an iron replacement product for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD) (United States Food and Drug Administration, June 2009). Potential uses of ferumoxytol extend beyond the treatment of iron deficiency anemia and may have important implications for hematology-oncology. Following administration, iron oxide nanoparticles initially serve as blood pool agents which is an ideal characteristic for assessing blood volume and blood flow. Subsequently, because of their long plasma half-life and ability to target inflammatory cells in the central nervous system (CNS), these compounds serve as excellent anatomic imaging agents. We have given adult patients with malignant CNS tumors and other CNS inflammatory lesions, ferumoxytol (n = 68) and ferumoxytran-10 [Combidex™’ (n = 97) as magnetic resonance (MR) contrast agents, on Institutional Review Board approved protocols. We hypothesize that iron oxide nanoparticles provide additional MR imaging information which may be beneficial in the differential diagnosis and in monitoring therapy in patients with CNS lesions. This report focuses on our experience with 16 patients with central nervous system lymphoma (CNSL). The patients underwent brain MR with gadolinium followed in 10 ± 9 days (mean ± SD) by MR with ferumoxytran-10 (2.6 mg/kg, intravenous [IV’ over 30 min) (n = 11) or ferumoxytol (510 mg, IV bolus) (n = 5). Findings of interest include: 1) in 3 patients, MR with iron oxide nanoparticles showed additional areas of CNS enhancement when compared with MR with gadolinium; 2) in 2 patients, increased enhancement patterns with iron oxide nanoparticles were diagnostically useful in distinguishing lymphoma from non-lymphomatous inflammatory conditions; and 3) in 2 patients with histories of CKD and post-renal transplant lymphoproliferative disorder confined to the CNS, MR with ferumoxytol was used to monitor therapy, as this agent appears to avoid the risk of nephrogenic systemic fibrosis (NSF), which is associated with exposure to gadolinium-containing contrast agents. Of note, in 1 patient with thromboembolic complications during therapy, brain MR enhancement was seen approximately 5 weeks after ferumoxytol infusion. The enhancement was initially interpreted as a hemorrhagic brainstem event and led to insertion of a superior vena cava filter rather than anticoagulation. This is an example of MR alteration which generally resolves in 3 to 5 days following ferumoxytol, however in rare instances may persist for up to 3 months. In summary, in addition to their use as iron replacement agents in iron deficiency anemia, the use of iron oxide compounds as MR contrast agents compliment the use of gadolinium. These agents offer exciting potential in the differential diagnosis of CNS inflammatory lesions versus CNSL, in monitoring CNS therapy, and may provide dual benefit in patients with CKD by possibly eliminating the gadolinium-associated risk of NSF.