Abstract

PurposeThe aim of this study was to determine the potential of magnetic resonance imaging to evaluate the biodistribution of exogenous iron within 24 h after one single injection of Venofer® (iron sucrose).MethodsVenofer® was evaluated in vitro for its ability to generate contrast in MR images. Subsequently, iron disposition was assessed in rats with MRI, in vivo up to 3 h and post mortem at 24 h after injection of Venofer®, at doses of 10- and 40 mg/kg body weight (n = 2 × 4), or saline (n = 4).ResultsWithin 10–20 min after injection of Venofer®, transverse relaxation rates (R2) clearly increased, representative of a local increase in iron concentration, in liver, spleen and kidney, including the kidney medulla and cortex. In liver and spleen R2 values remained elevated up to 3 h post injection, while the initial R2 increase in the kidney was followed by gradual decrease towards baseline levels. Bone marrow and muscle tissue did not show significant increases in R2 values. Whole-body post mortem MRI showed most prominent iron accumulation in the liver and spleen at 24 h post injection, which corroborated the in vivo results.ConclusionsMR imaging is a powerful imaging modality for non-invasive assessment of iron distribution in organs. It is recommended to use this whole-body imaging approach complementary to other techniques that allow quantification of iron disposition at a (sub)cellular level.

Highlights

  • Iron is an essential nutrient for the transport of oxygen in the body

  • Pharm Res (2018) 35: 88 patients suffering from disorders such as chronic kidney disease (CDK) are in need of treatments such as erythropoietin and/or intravenous iron to enhance the number of erythrocytes [1,2,3]

  • Several FDA-approved iron products are presently used in clinical practice, of which iron sucrose has been widely used because this complex has shown to induce less side effects compared to other first generation intravenous iron complexes such as high molecular weight iron dextran [4,5]

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Summary

Introduction

Iron is an essential nutrient for the transport of oxygen in the body. It is mainly present in heme, which is an important component of the oxygen-transporting protein hemoglobin that is present in erythrocytes. The iron complexes which are colloidal dispersions of polynuclear ferric-oxyhydroxide cores stabilized by a carbohydrate shell, are taken up by phagocytosis by macrophages of the mononuclear phagocyte system (previously termed reticuloendothelial system (RES)) [8]. In case of iron overload, accumulation of iron in macrophages represents a safety concern as this might result in oxidative stress, inflammation, kidney- and heart disorders [6,14] Because of these safety concerns, there is a great need for insight into the distribution of iron after intravenous administration of ironbased medicinal products. Beshara et al studied the long-term kinetics and distribution of iron after an intravenous injection, with a particular focus on iron distribution and the production of erythrocytes within 3–4 weeks after administration [16]

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