Relaxivity and In Vivo Human Performance of Brand Name Versus Generic Ferumoxytol.

Abstract

Ferumoxytol is a superparamagnetic iron-oxide product that is increasingly used off-label for contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). With the recent regulatory approval of generic ferumoxytol, there may be an opportunity to reduce cost, so long as generic ferumoxytol has similar imaging performance to brand name ferumoxytol. This study aims to compare the relaxation-concentration dependence and MRI performance of brand name ferumoxytol with generic ferumoxytol through phantom and in vivo experiments. The secondary purpose was to determine the optimal flip angle and optimal weight-based dosing. Phantom experiments were performed using both brand name (AMAG Pharmaceuticals) and generic (Sandoz Pharmaceuticals) ferumoxytol products. Each ferumoxytol product was diluted in saline, and separately in adult bovine whole blood, at 5 iron concentrations ranging from 0.3 to 2.1 mM. Vials were placed in an MR-compatible water bath at 37°C and imaged at both 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured for each ferumoxytol concentration, and relaxation-concentration curves were estimated. An in vivo dose accumulation study with flip angle optimization was also implemented using a cross-over design, in healthy volunteers. Cumulative doses of 1, 3, 5, and 7 mg/kg diluted ferumoxytol were administered prior to MRA of the chest on a 3.0 T clinical MRI system. For each incremental dose, the flip angle was varied from 40° to 10° in -10° increments over 5 breath-holds followed by a repeated 40° flip angle acquisition. Regions of interest were drawn in the aortic arch, paraspinous muscles, and a noisy area outside of the patient, free from obvious artifact. Signal-to-noise ratio (SNR) was calculated as the quotient of the average signal in the aortic arch and the standard deviation of the noise, corrected for a Rician noise distribution. Contrast-to-noise ratio was calculated as the difference in SNR between the aorta and paraspinous muscles. Absolute SNR and contrast-to-noise ratio values were compared between products for different flip angles and doses. There were no statistically significant or clinically relevant differences in relaxation-concentration curves between AMAG and Sandoz products in phantom experiments. Six healthy volunteers (38.8 ± 11.5 years, 3 female, 3 male) were successfully recruited and completed both imaging visits. No clinically relevant differences in image quality were observed between ferumoxytol products. The optimal flip angle range and dose for both products was 20°-30° and 5 mg/kg, respectively. Brand name and generic ferumoxytol products can be used interchangeably for MRA.