MR nanoparticle contrast targets angiogenic markers of atherosclerosis

CONTEXT: As atherosclerotic plaque invades the arterial wall, it develops a network of tiny new blood vessels. The integrin avBeta3 is a marker for angiogenesis and therefore represents an attractive target for molecular imaging aimed at the early identification of vulnerable and inflamed plaque.

RESULTS: Investigators at Washington University School of Medicine in St. Louis developed a nanoparticle targeted against avBeta3-integrin by incorporating hundreds of tailor-made peptide-like particles into its lipid outer layer. Also linked to each nanoparticle were some 90,000 molecules of gadolinium DTPA to enable detection by MR.

Patrick M. Winter, Ph.D., and colleagues injected the nanoparticles intravenously into atherosclerotic, cholesterol-fed rabbits. Using a 1.5T clinical MR scanner and T1-weighted imaging, they detected increased angiogenesis throughout the wall of the abdominal aorta in rabbits injected with integrin-targeted paramagnetic nanoparticles. On average, signal intensity increased by 47% at two hours. For comparison, rabbits were also injected with nontargeted paramagnetic particles; signal enhancement averaged just 26%. Equally important, pretreatment of the rabbits with integrin-targeted nonparamagnetic nanoparticles reduced contrast enhancement by at least 50% through competitive blocking, thus demonstrating the specificity of the nanoparticle's integrin targeting.

IMAGE: MR contrast enhancement appears in the cholesterol-fed rabbits two hours after injection with avBeta3-integrin in renal artery (A), mid-aorta (B), and diaphragm (C). (Provided by P. Winter; reprinted with permission from Circulation 2003;108:227-2274.)

IMPLICATIONS: The use of this novel paramagnetic nanoparticle may enable physicians not only to identify arterial plaque through its angiogenic blood supply, but also to track the effectiveness of anti-atherosclerosis therapies.