Angiotensin II subtype 1 receptor imaging in renal ischemia reperfusion

Objectives The renal angiotensin system (RAS) mediates important mechanisms of ischemic nephropathy including inflammation, fibrosis and tubular injury. Aim of this study was to investigate the angiotensin II subtype 1 receptor (AT1R) as a potential molecular imaging biomarker of renal injury in animal models of acute ischemia, chronic ischemia and ischemia reperfusion.

Methods Domestic pigs (Sus domestica) were divided into 4 groups: control (n=6), one week after acute renal artery occlusion / reperfusion (n=5), chronic renal artery stenosis (n=7), chronic renal artery stenosis treated with a stent (n=5). Renal artery stenosis was diagnosed by magnetic resonance angiography. Renal perfusion was assessed using the first minute accumulation of [C-11]KR31173 (area under curve) and was validated with O-15 water PET. AT1R binding was quantified with the retention of [C 11]KR31173 and was validated with in vitro autoradiography. Data were displayed as [median (interquartile range)].

Results One week after acute ischemia reperfusion AT1R binding [0.15(0.15-0.18)] was similar to control [0.19(0.13-0.25)]. AT1R binding was increased in chronic stenosis both without [0.23(0.17-0.30)] and with [0.32(0.23-0.41)] stenting. Overall, decreased renal perfusion correlated with increased in vivo AT1R binding (r=-0.626, p<0.001). Correlation between the in vivo and in vitro binding parameters was significant (r=0.405, p< 0.02).

Conclusions Reduced renal perfusion results in increased AT1R binding which does not return to normal after stent treatment indicating activation of the RAS for an extended period of time. Positive correlation between in vivo and in vitro binding parameters supports the use of [C 11]KR31173/PET for investigation of the AT1R in renal ischemia and reperfusion.

Research Support Supported by National Institute of Diabetes and Digestive and Kidney Diseases grant RO1 DK50183