Relaxivity of Ferumoxytol at 1.5 T and 3.0 T

Objectives The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Materials and Methods Ferumoxytol was diluted in gradually increasing concentrations (0.26–4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. Results A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 s−1mM−1; r1plasma = 19.0 ± 1.7 s−1mM−1; r2saline = 60.8 ± 3.8 s−1mM−1; r2plasma = 64.9 ± 1.8 s−1mM−1; r2*saline = 60.4 ± 4.7 s−1mM−1; r2*plasma = 64.4 ± 2.5 s−1mM−1; 3.0 T: r1saline = 10.0 ± 0.3 s−1mM−1; r1plasma = 9.5 ± 0.2 s−1mM−1; r2saline = 62.3 ± 3.7 s−1mM−1; r2plasma = 65.2 ± 1.8 s−1mM−1; r2*saline = 57.0 ± 4.7 s−1mM−1; r2*plasma = 55.7 ± 4.4 s−1mM−1). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Conclusions Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

[1]  N. Rofsky,et al.  MR imaging relaxation times of abdominal and pelvic tissues measured in vivo at 3.0 T: preliminary results. , 2004, Radiology.

[2]  M. Prince,et al.  A pilot investigation of new superparamagnetic iron oxide (ferumoxytol) as a contrast agent for cardiovascular MRI. , 2003, Journal of X-ray science and technology.

[3]  V. Magnotta,et al.  The Emerging Role of Ferumoxytol-Enhanced MRI in the Management of Cerebrovascular Lesions , 2013, Molecules.

[4]  J. Finn,et al.  Cardiovascular MRI with ferumoxytol. , 2016, Clinical radiology.

[5]  V. Magnotta,et al.  Imaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: preliminary results. , 2013, Journal of neuroradiology. Journal de neuroradiologie.

[6]  S. Schoenberg,et al.  Can Ferumoxytol be Used as a Contrast Agent to Differentiate Between Acute and Chronic Inflammatory Kidney Disease?: Feasibility Study in a Rat Model , 2016, Investigative radiology.

[7]  Tyler J. Fraum,et al.  Gadolinium‐based contrast agents: A comprehensive risk assessment , 2017, Journal of magnetic resonance imaging : JMRI.

[8]  R. Pazdur,et al.  FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease , 2010, American journal of hematology.

[9]  Linda M. Johnson,et al.  A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer. , 2015, AJR. American journal of roentgenology.

[10]  R. Weissleder,et al.  Utility of a new bolus-injectable nanoparticle for clinical cancer staging. , 2007, Neoplasia.

[11]  C. Batich,et al.  Materials Characterization of Feraheme/Ferumoxytol and Preliminary Evaluation of Its Potential for Magnetic Fluid Hyperthermia , 2013, International journal of molecular sciences.

[12]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[13]  C. Springer,et al.  Human whole blood 1H2O transverse relaxation with gadolinium‐based contrast reagents: Magnetic susceptibility and transmembrane water exchange , 2017, Magnetic resonance in medicine.

[14]  S. Reeder,et al.  Multipeak fat‐corrected complex R2* relaxometry: Theory, optimization, and clinical validation , 2013, Magnetic resonance in medicine.

[15]  S. Reeder,et al.  Mathematical optimization of contrast concentration for t1‐weighted spoiled gradient echo imaging , 2016, Magnetic resonance in medicine.

[16]  S E Seltzer,et al.  Hepatic MR imaging with ferumoxides: a multicenter clinical trial of the safety and efficacy in the detection of focal hepatic lesions. , 1995, Radiology.

[17]  Fernando Calamante,et al.  Gadolinium deposition in the brain: summary of evidence and recommendations , 2017, The Lancet Neurology.

[18]  John N Morelli,et al.  T1 Relaxivities of Gadolinium-Based Magnetic Resonance Contrast Agents in Human Whole Blood at 1.5, 3, and 7 T , 2015, Investigative radiology.

[19]  Daniele Marin,et al.  Emerging applications for ferumoxytol as a contrast agent in MRI , 2015, Journal of magnetic resonance imaging : JMRI.

[20]  A. Kausz,et al.  Ferumoxytol for treating iron deficiency anemia in CKD. , 2008, Journal of the American Society of Nephrology : JASN.

[21]  Philippe Robert,et al.  Recent advances in iron oxide nanocrystal technology for medical imaging. , 2006, Advanced drug delivery reviews.

[22]  J. Balschi,et al.  Active trans-plasma membrane water cycling in yeast is revealed by NMR. , 2011, Biophysical journal.

[23]  Wei Li,et al.  First‐pass contrast‐enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)‐based blood pool agent , 2005, Journal of magnetic resonance imaging : JMRI.