Abstract 2945: Assessment of Transient Myocardial Alpha(v)beta(3) Integrin Expression after Ischemia by PET
Background: Alpha(v)beta(3) integrin is thought to play a critical role in migration and adhesion of endothelial cells during myocardial angiogenesis after ischemia. We assessed the feasibility of a new PET imaging approach using a [F-18]-labeled alpha(v)beta(3) integrin antagonist ([F-18]gRGD) to monitor the integrin expression in a rat model of myocardial ischemia.
Methods and results: Rats (n=51) were subjected to 20 minutes of transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis was used to determine myocardial [F-18]gRGD uptake at different time points after reperfusion. Autoradiography yielded no significant focal myocardial [F-18]gRGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the area at risk started at 3 days (mean uptake ratio=1.91), peaked between one (3.43) and 3 weeks (3.43), and decreased to 1.96 at 6 months after reperfusion. In vivo imaging by PET yielded quantitative measurements of tracer uptake. Pretreatment with 18mg/kg c(RGDfV) significantly decreased the tracer uptake indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis.
Conclusions: Regional [F-18]gRGD accumulation suggests up regulation of alpha(v)beta(3) integrin expression in ischemic myocardium, which peaks between 1 and 3 weeks and remains detectable until 6 months after ischemia. This new tracer technique in combination with PET is promising for the quantitative monitoring of myocardial repair processes as well as the assessment of efficacy in angiogenesis therapies.