4.5 Article

The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats

Journal

PHARMACEUTICAL RESEARCH
Volume 35, Issue 4, Pages -

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-018-2348-y

Keywords

biodistribution; intravenous; iron; MRI; oxidative stress

Funding

  1. Vifor (International) Ltd., St. Gallen, Switzerland

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Purpose The 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 (R) (iron sucrose). Methods Venofer (R) 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 (R), at doses of 10and 40 mg/kg body weight (n = 2 x 4), or saline (n = 4). Results Within 10-20 min after injection of Venofer (R), transverse relaxation rates (R-2) dearly increased, representative of a local increase in iron concentration, in liver, spleen and kidney, including the kidney medulla and cortex. In liver and spleen R-2 values remained elevated up to 3 h post injection, while the initial R-2 increase in the kidney was followed by gradual decrease towards baseline levels. Bone marrow and musde tissue did not show significant increases in R-2 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. Conclusions MR 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.

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