Molecular imaging and therapy directed at the neovasculature in pathologies

Abstract

We have discussed the impact of molecular imaging on clinical and preclinical medicine. We have presented the potential problems of delivering the effective therapeutic dose and the properties that can help contribute to the drug efficacy. The rationale for the design of new antiangiogenic agents that can be used for imaging and therapy was presented. Finally, results from imaging and targeted nanoparticle based therapies were presented. In vivo imaging of angiogenic tumors using anti-alpha(v)beta3 -targeted polymerized vesicles composed of the murine antibody LM609 attached to NPs labeled with the MR contrast agent gadolinium in the V2 carcinoma model in rabbits. MRI studies using this targeted contrast agent revealed large areas of alpha(v)beta3 integrin expression in tumor-associated vasculature that conventional MRIs failed to show. Other investigators have used microemulsions conjugated to an antibody targeted against alpha(v)beta as imaging agents. These materials also show contrast enhancement of tumor vasculature undergoing angiogenesis. Other markers, such as the PECAM-1 (CD-31), VCAM-1 (CD54) and VEGF receptor (flk-1), have been shown to be upregulated on tumor endothelium and associated with angiogenesis but have not been used in imaging studies. Furthermore, by modification of the NPs, we were able to use this imaging agent as an antiangiogenic gene delivery system. The results from these studies are very promising and are being further pursued.