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In-vivo magnetic resonance imaging of renal ischaemia/reperfusion injury using microparticles of iron oxide targeting vascular cell adhesion molecule 1
  1. AM Akhtar,
  2. JE Schneider,
  3. MA McAteer,
  4. S Chapman,
  5. H Barnes,
  6. JE Digby,
  7. K Wood,
  8. RP Choudhury
  1. University of Oxford, Oxford, UK

Abstract

Introduction Ischaemia/reperfusion injury (IRI) is an important cause of tissue damage in vascular syndromes of the heart, brain and kidney. Sensitive tools to image ischaemic injury non-invasively are lacking. We hypothesised that antibody-conjugated microparticles of iron oxide (MPIO) targeting vascular cell adhesion molecule 1 (VCAM-1) would enable molecular magnetic resonance imaging (MRI) of endothelial activation in a mouse model of renal IRI.

Methods and Results MPIO (1.0 μm) were conjugated to monoclonal antibody against vascular cell adhesion molecule 1 (VCAM–MPIO). In male C57BL/6 mice (n  =  10) the left renal pedicle was cross-clamped for 30 minutes to induce IRI. Following 12 h reperfusion, mice were anaesthetised with isofluorane and administered intravenously with VCAM–MPIO (n  =  5) or negative control IgG–MPIO (n  =  3). In-vivo MRI (9.4T) was performed for 90 minutes. VCAM–MPIO binding produced low signal areas in the clamped kidney, with little retention in the contra lateral unclamped kidney. Significant VCAM–MPIO binding to the endothelium was observed in ischaemic kidneys compared with the negative control IgG–MPIO (p<0.01). Pretreatment of mice with VCAM-1 antibody 30 minutes before VCAM–MPIO administration abolished the retention of VCAM–MPIO in ischaemic kidneys. All mice tolerated MPIO administration well, with rapid sequestration in the liver and spleen (see figs 1 and 2).

Conclusion (1) In a mouse model of renal IRI in vivo, VCAM–MPIO bound specifically and under flow conditions. (2) Retained MPIO were readily quantifiable by MRI. (3) This provides a platform for non-invasive detection of IRI in the kidney and other organs.

Abstract 030 Figure 1

MPIO, microparticles of iron oxide; MRI, magnetic resonance imaging; VCAM, vascular cell adhesion molecule.

Abstract 030 Figure 2

3D reconstruction of ischaemic and non-ischaemic kidneys using automated histogram based segmentation (vascular cell adhesion molecule (VCAM) microparticles of iron oxide (MPIO) shown in green, renal artery shown in red).

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