A review: Integrin α_vβ₃-targeted molecular imaging and therapy in angiogenesis

Integrin α_vβ₃ provides numerous possibilities for diagnostic imaging probes and therapeutic potentials for angiogenesis research. There has been significant advancement since it was first discovered as an endothelial marker responsible for angiogenesis. There are hundreds of patents and publications on integrin α_vβ₃ targeting antibodies, peptides, and peptidomimetics. Additionally, ligand array of integrin antagonists on nanoparticles has proven a viable strategy to target vascular surface receptors on endothelial cells. The results of ongoing clinical trials of the two most advanced α_vβ₃-integrin antagonists, Vitaxin and Cilengitide, are enthusiastically awaited for further drug discovery research efforts of other antiangiogenic drugs. More recent development of small peptidomimetic molecules modified for obtaining more selective targeting has provided ligands with higher binding affinity. Preclinical studies with these synthetic ligands are promising, and there is continued effort to modify these ligands to improve pharmacokinetics and imaging characteristics for the development of imaging probes and therapeutic agents. Synergistic effects seen with polyvalent materials are being pursued by making multivalent molecules. Considerable advances in nanoparticle research has enabled us to further optimize controlled delivery as well as site-specific delivery. This multivalent nanoparticle technology combined with high-affinity, target-specific ligands would further help achieve high selectivity, increased receptor affinity, and improved tracer properties through multilevel synergy. Moreover, the use of this targeting system as vectors for drug delivery will significantly increase selectivity to the target without undesirable systemic toxicity. As translation of these integrin-targeting approaches toward clinical settings progresses, potential uses of these imaging and therapeutic agents in the clinic will soon become a reality.