Abstract 16488: Thrombin-Inhibiting Perfluorocarbon Nanoparticles Reduce Intrarenal Coagulation in Acute Kidney Injury and Provide Image-Based Readouts (19F MRI) of Renal Endothelial Disruption
Introduction: Endothelial damage is a crucial component of acute kidney injury (AKI). We sought to utilize perfluorocarbon nanoparticle (PFC NP) as both a therapeutic and diagnostic vehicle incorporating direct thrombin-inhibitor, Phe[D]-Pro-Arg-Chloromethylketone (PPACK), to inhibit intrarenal vessel coagulation. The 19F signal emanating from PFC NP also would enable non-invasive detection of endothelial damage that incites focal thrombosis.
Method: Male C57BL/6 mice were used for the study and all MRI was performed at an 11.7 T animal scanner. Animals (n = 10) underwent unilateral renal ischemia by complete ligation of the left renal artery and vein for 60 minutes followed by reperfusion. PFC NP was injected intravenously 24 hours post initial injury for 19F MRI. To assess the treatment effect of PPACK PFC NPs, another group of animals were injected with PPACK PFC NPs (n = 3) or plain PFC NPs (n = 3) at 15 minutes before experiencing 60 minutes ischemia. At 3 hours after reperfusion, animals were euthanized and perfused with saline. Kidneys were then excised for 19F MRI and quantification.
Result: Fig. a&b show 19F MR images of an injured versus its contralateral control kidney. Enhanced 19F signal intensity at the medulla indicates extensive microvascular damage in this region (c). After treatment with PPACK or plain PFC NPs, composite 1H/19F images showed less 19F signal (color coded) emanating from trapped NPs in an injured kidney treated with therapeutic PPACK PFC NPs (d) versus an injured kidney treated with plain PFC NPs (e). This observation was confirmed by 19F MRI quantified concentration of trapped NPs (f).
Conclusion: PPACK PFC NPs effectively inhibit coagulation in AKI in small quantities, as evidenced by lesser accumulation of particles trapped by the clotting process, which suggests a new strategy for treating and evaluating kidney endothelial damage with thrombin targeted19F MRI.
- © 2012 by American Heart Association, Inc.