Microarray search for radiation-induced markers for vascular targeting of brain AVM tissues

Brain arteriovenous malformations (AVMs) are abnormalities of blood vessels, in which direct connections form between arteries and veins. The high-pressure arterial blood injects into fragile cerebral veins and results in a high risk of bleeding (stroke). AVMs occur in approximately 0.1% of the population and affect predominantly children and young adults.

Current treatments are removing the abnormal vessels (surgery) or blocking the blood flow (injection of blocking material inside the vessels or irradiation of the AVMs), aiming to prevent bleeding. The methods have limitations and no effective treatment is available for large and deep AVMs.

‘Vascular targeting’ is a technique of deliberate induction of localised blood clotting (thrombosis) utilizing molecular differences between AVM vessels and normal vessels. This can be achieved by specific binding of antibodies linked with thrombotic reagents to the unique molecules (markers) on the AVM vessels. Although these markers have not been identified, radiation has the potential to induce specific molecule changes on the vessels, which can be used as markers for vascular targeting of these lesions.

In this work, we will use a state-of-the-art molecular analysis technique (microarray) to screen the radiation-induced markers on the surface of cells lining AVM vessels and identify their binding partners (ligands) simultaneously. Microarrays have large number of ligands immobilized in precise positions on their surfaces. If an irradiated cell carries specific markers on its surface, it will bind to the corresponding ligand areas, leading to the identification of the markers and their ligands.

The ligands will be chemically linked with a thrombotic agent and used as vascular-targeting agents for irradiated AVM vessels in future studies. Successful development of the technique will provide an effective treatment for AVMs.