Towards non-invasive imaging of vulnerable atherosclerotic plaques by targeting co-stimulatory molecules

- We analyzed human stable and vulnerable carotid endarterectomy plaques.
- CD80 and CD86 are significantly upregulated in vulnerable plaques.
- A high affinity molecule for CD80 was radiolabeled with carbon-11 ([11C]7).
- In vitro autoradiography revealed higher binding of [11C]7 to vulnerable plaques.
- We report an important step towards non-invasive imaging of vulnerable plaques.

BackgroundMyocardial infarction and stroke are the life-threatening consequences after plaque rupture in coronary or carotid arteries. Positron emission tomography employing [18F]fluorodeoxyglucose can visualize plaque inflammation; however, the question remains whether this is specific for plaque vulnerability. The pathophysiology of vulnerable plaques suggests several molecular processes. Here, we propose the co-stimulatory molecules CD80 and CD86 as potential new targets for non-invasive imaging.Methods and resultsHuman atherosclerotic segments were obtained from carotid endarterectomy and classified into stable and vulnerable plaques. We identified CD80 and CD86 with significantly higher mRNA levels in vulnerable than stable plaques. CD80 + and CD86 + cells were found in spatial proximity to CD83 + dendritic cells and CD68 + macrophages of atherosclerotic plaques. As a proof of target-expression we labeled a low molecular weight ligand, which has a high affinity for human CD80, with carbon-11 to perform in vitro autoradiography with human plaque slices. We observed 3-fold higher binding to vulnerable than stable plaques, demonstrating a first approach towards discriminating between the two plaque types. Positron emission tomography studies showed accumulation in CD80 + Raji xenografts, low radioactivity in myocardium and rapid clearance from the blood pool in mice.ConclusionIn human carotid arteries, the co-stimulatory molecules CD80 and CD86 show significantly higher expression levels in vulnerable compared to stable plaques. With the novel CD80-specific radiotracer we are able to discriminate between stable and vulnerable atherosclerotic plaques in vitro. This is an important step towards non-invasive imaging of the life-threatening vulnerable lesions in humans.