Molecular imaging of angiogenesis

Angiogenesis, the process whereby new capillaries are formed by outgrowth from existing microvessels, is required for tumor growth and metastasis, as well as for healing of ischemic injuries. Because angiogenesis is a promising target for molecular therapies, there is a real need to develop molecular imaging methods to monitor angiogenesis activity. Direct imaging of angiogenesis can help define the pathophysiology of angiogenic processes in vivo, and foster personized medicine by identifying patients likely to respond to angiogenesis-targeted drugs and accurately monitor the therapeutic efficacy. Promising imaging targets include integrins, vascular endothelial growth factor (VEGF) receptors, and matrix metalloproteinases. While MRI and optical imaging modalities are also workable, radiolabeled RGD (arginine-glycine-aspartate) probes that target α_vβ₃ integrins overexpressed on activated endothelia are the most extensively investigated and successful angiogenesis imaging technique to date. This technique has repeatedly been validated in preclinical models of cancers and ischemic diseases, and clinical studies are presently ongoing to elucidate the value of RGD positron image tomography (PET) imaging in human patients. Herein, we review the current status of angiogenesis imaging research with special emphasis on integrin-targeted techniques.