Comparison of Three Ultrasmall, Superparamagnetic Iron Oxide Nanoparticles for MRI at 3.0 T

Abstract

Background: The ultrasmall, superparamagnetic iron oxide (USPIO) nanoparticle ferumoxytol has unique applications in cardiac, vascular, and body magnetic resonance imaging (MRI) due to its long intravascular half-life and suitability as a blood pool agent. However, limited availability and high cost have hindered its clinical adoption. A new ferumoxytol generic, and the emergence of MoldayION as an alternative USPIO, represent opportunities to expand the use of USPIO-enhanced MRI techniques.

Purpose: To compare in vitro and in vivo MRI relaxometry and enhancement of Feraheme, generic ferumoxytol, and MoldayION.

Study type: Prospective.

Animal model: Ten healthy swine and six swine with artificially induced coronary narrowing underwent cardiac MRI.

Field strength/sequence: 3.0 T; T1-weighted (4D-MUSIC, 3D-VIBE, 2D-MOLLI) and T2-weighted (2D-HASTE) sequences pre- and post-contrast.

Assessment: We compared the MRI relaxometry of Feraheme, generic ferumoxytol, and MoldayION using saline, plasma, and whole blood MRI phantoms with contrast concentrations from 0.26 mM to 2.10 mM. In-vivo contrast effects on T1- and T2-weighted sequences and fractional intravascular contrast distribution volume in myocardium, liver, and spleen were evaluated.

Statistical tests: Analysis of variance and covariance were used for group comparisons. A P value <0.05 was considered statistically significant.

Results: The r₁ relaxivities for Feraheme, generic ferumoxytol, and MoldayION in saline (22 °C) were 7.11 ± 0.13 mM^-1 s^-1 , 8.30 ± 0.29 mM^-1 s^-1 , 8.62 ± 0.16 mM^-1 s^-1 , and the r₂ relaxivities were 111.74 ± 3.76 mM^-1 s^-1 , 105.07 ± 2.20 mM^-1 s^-1 , and 109.68 ± 2.56 mM^-1 s^-1 , respectively. The relationship between contrast concentration and longitudinal (R1) and transverse (R2) relaxation rate was highly linear in saline and plasma. The three agents produced similar in vivo contrast effects on T1 and T2 relaxation time-weighted sequences.

Data conclusion: Relative to clinically approved ferumoxytol formulations, MoldayION demonstrates minor differences in in vitro relaxometry and comparable in vivo MRI characteristics.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 1.

Keywords: intravascular contrast agents; iron-based contrast agents; relaxometry; theranostics; ultrasmall superparamagnetic iron oxides.