Intra-arterial in-situ bevacizumab injection effect on angiogenesis. Results on a swine angiogenesis model

Background and purpose: In this study we tested the effect of antiangiogenics on a swine angiogenesis model that shares some brain AVM histological characteristics. The objective was to determine bevacizumab effects on retia volumes and on vessels' wall.

Materials and methods: Fifteen pigs were divided into 3 groups: Five animals served as controls (group A), 5 animals underwent endovascular left external and common carotid artery occlusion (group B) and 5 animals underwent the same procedure and had an intra-arterial in-situ injection of bevacizumab (groupC) 2 months after the occlusion. A DSA associated with 3D-rotational angiography was performed at day 0 and at 3 months in all groups in order to measure rete mirabile volumes. The animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations.

Results: All VEGF-A receptors were blocked at the site of injection and there was a local enhanced endothelial proliferation and apoptosis. The volume of the retia remained unchanged after the bevacizumab injection. Retia vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection.

Conclusion: A single in-situ injection of bevacizumab in this swine angiogenesis model showed no change in retia volume and an extensive blockage of VEGF receptors at the site of injection one month later. Rete mirabile vessels presented comparable media thickness, higher endothelial proliferation and apoptosis after the anti-VEGF injection, suggesting that bevacizumab antiangiogenic effect does not fragilize vessel wall. More studies are needed to confirm these preliminary insights of in-situ antiangiogenic effect on vascular malformations.