TY - JOUR
T1 - The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats
AU - Span, Kimberley
AU - Pieters, Ebel H.E.
AU - Hennink, Wim E.
AU - van der Toorn, Annette
AU - Brinks, Vera
AU - Dijkhuizen, Rick M.
AU - van Tilborg, Geralda A.F.
N1 - Funding Information:
This research was financially supported by Vifor (International) Ltd., St. Gallen, Switzerland.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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® (iron sucrose). Methods: Venofer® 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). Results: Within 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. 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.
AB - 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® (iron sucrose). Methods: Venofer® 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). Results: Within 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. 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.
KW - biodistribution
KW - intravenous
KW - iron
KW - MRI
KW - oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85043325815&partnerID=8YFLogxK
U2 - 10.1007/s11095-018-2348-y
DO - 10.1007/s11095-018-2348-y
M3 - Article
AN - SCOPUS:85043325815
SN - 0724-8741
VL - 35
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 4
M1 - 88
ER -