Pharmacokinetics of Ferumoxytol in the Abdomen and Pelvis: A Dosing Study with 1.5- and 3.0-T MRI Relaxometry.

Abstract

Background The off-label use of ferumoxytol (FE), an intravenous iron preparation for iron deficiency anemia, as a contrast agent for MRI is increasing; therefore, it is critical to understand its pharmacokinetics. Purpose To evaluate the pharmacokinetics of FE in the abdomen and pelvis, as assessed with quantitative 1.5- and 3.0-T MRI relaxometry. Materials and Methods R2*, an MRI technique used to estimate tissue iron content in the abdomen and pelvis, was performed at 1.5 and 3.0 T in 12 healthy volunteers between April 2015 and January 2016. Volunteers were randomly assigned to receive an FE dose of 2 mg per kilogram of body weight (FE2mg) or 4 mg/kg (FE4mg). MRI was repeated at 1.5 and 3.0 T for each volunteer at five time points: days 1, 2, 4, 7, and 30. A radiologist experienced in MRI relaxometry measured R2* in organs of the mononuclear phagocyte system (MPS) (ie, liver, spleen, and bone marrow), non-MPS anatomy (kidney, pancreas, and muscle), inguinal lymph nodes (LNs), and blood pool. A paired Student t test was used to compare changes in tissue R2*. Results Volunteers (six female; mean age, 44.3 years ± 12.2 [standard deviation]) received either FE2 mg (n = 5) or FE4 mg (n = 6). Overall R2* trend analysis was temporally significant (P < .001). Time to peak R2* in the MPS occurred on day 1 for FE2mg and between days 1 and 4 for FE4mg (P < .001 to P < .002). Time to peak R2* in non-MPS anatomy, LNs, and blood pool occurred on day 1 for both doses (P < .001 to P < .09). Except for the spleen (at 1.5 T) and liver, MPS R2* remained elevated through day 30 for both doses (P = .02 to P = .03). Except for the kidney and pancreas, non-MPS, LN, and blood pool R2* returned to baseline levels between days 2 and 4 at FE2mg (P = .06 to P = .49) and between days 4 and 7 at FE4mg (P = .06 to P = .63). There was no difference in R2* change between non-MPS and LN R2* at any time (range, 1-71 sec-1 vs 0-50 sec-1; P = .06 to P = .97). Conclusion The pharmacokinetics of ferumoxytol in lymph nodes are distinct from those in mononuclear phagocyte system (MPS) organs, parallel non-MPS anatomy, and the blood pool. © RSNA, 2019 Online supplemental material is available for this article.