A new imaging method has been used to successfully identify miniscule, young blood vessels that form during the development of plaques, according to a new study by researchers at Washington University School of Medicine in St. Louis, MO. These plaques are akin to atherosclerosis in humans, the primary cause of heart attack and stroke.
‘We’ve developed a way to take non-invasive images of very early plaques, before they’re detectable by any other means,’ says Dr. Samuel A. Wickline, professor of medicine and biomedical engineering. ‘This same technology, we think, will allow us to detect very early cancers and other inflammatory events as well.’
Atherosclerosis – the progressive hardening of arteries – results from the accumulation of plaques in key blood vessels. In order for plaques to form, a crowd of smaller vessels, called capillaries, must develop around the diseased site.
In the study, the team used a relatively new imaging method – developed primarily at Washington University – to label growing capillaries, thereby identifying locations where plaques are about to form. They loaded an extremely small particle roughly 200 nanometers long, called a nanoparticle, with about 80,000 atoms of gadolinium, which shows up as a bright spot on a magnetic resonance image (MRI).
In order to ensure that gadolinium highlighted only new capillaries, the team also packed the nanoparticle with molecules that specifically detect a protein called avb3, which is abundant in rapidly growing capillaries. In so doing, the nanoparticles mainly latched onto cells that contain avb3.
‘You can load these nanoparticles with whatever you want,’ Wickline explains. ‘The targeting agent allows us to select where the particle goes, and then we can either add an imaging agent, like gadolinium, or a drug, like plaque stabilising medications or anticancer agents.’
The team injected nanoparticles loaded with avb3 detectors and gadolinium into 13 rabbits. Four of the rabbits had been fed normal diets and nine had been fed high-cholesterol diets for about 80 days. They then took MRI scans of the abdominal aorta – the largest artery in the body – for two hours after injection. The cholesterol-fed rabbits injected with targeted nanoparticles had more than twice as much gadolinium in their abdominal aorta than the other rabbits.
Post-mortem examination confirmed that the cholesterol-fed animals were in fact developing dangerous capillaries around the aorta, in contrast to the control diet rabbits.
‘These preliminary results suggest that we can manipulate nanoparticles to image plaques as they are just beginning to form,’ says Wickline. ‘Previous research of ours also suggests that this technique can distinguish between patients with stable plaques from those whose plaques are about to rupture and thereby cause a heart attack or stroke.’
Because tumours also require new populations of capillaries, the team believes this technique will enable them to detect very early cancers at the beginning stages of tumour development.
The technology used in the study has been licensed to KEREOS Incorporated, which is devoted to molecular imaging and targeted therapeutics.