In vivo quantification of VCAM-1 expression in renal ischemia reperfusion injury using non-invasive magnetic resonance molecular imaging.

Vascular cell adhesion molecule-1 (VCAM-1) is upregulated in ischemia reperfusion injury (IRI), persisting after restoration of blood flow. We hypothesized that microparticles of iron oxide targeting VCAM-1 (VCAM-MPIO) would depict "ischemic memory" and enable in vivo assessment of VCAM-1 expression. Mice subject to unilateral, transient (30 minutes) renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO (4.5 mg iron/kg body weight). Contrast agent bound rapidly (<30 minutes) in IRI-kidneys and appeared as intensely low signal areas by MRI in vivo. Automated segmentation and quantification yielded MPIO contrast volumes of 5991±354×10(6) μm(3) in IRI vs. 87±7×10(6) μm(3) in kidneys with no surgical intervention (P<0.001); 90±8×10(6) μm(3) in IRI kidneys exposed to control (IgG-MPIO) and 625±80×10(6) μm(3), in IRI kidneys pre-treated with a blocking dose of VCAM-1 antibody (P<0.001). In keeping with quantitative MRI data, VCAM-1 mRNA expression in IRI was 65-fold higher than in kidneys without surgical intervention (3.06±0.63 vs. 0.05±0.02, P<0.001). Indeed VCAM-1 mRNA expression and VCAM-MPIO contrast volume were highly correlated (R(2)=0.901, P