The primary goal of this proposal is to develop a de novo lectin-targeted imaging probe that improves our ability to image the structural and functional changes in tumor blood vessels during angiogenesis, using molecular magnetic resonance imaging (MRI). We propose to develop a dual-modality (MRI and optical) contrast agent targeted to the lumen of blood vessels using the lectin from Bandeiraea Simplicifolia (GS-1), a protein of non-immune origin that binds to endothelial cells, for up to 18h in vivo without extravasating from tumor vessels.
Aim 1 is focused on developing a T1 liposome-based lectin-targeted contrast agent, while Aim 2 focuses on developing a T2 superparamagnetic lectin-targeted nanoparticle based contrast agent. With these new contrast agents, we intend to characterize the remodeling of the vascular architecture that accompanies tumor progression, in a human metastatic breast cancer model. We will do this in vivo using high-resolution 3D MRI, and for the first time ex vivo using MR microscopy (}MRI), producing the very first 3D }digital casts} of the vessel architecture. The fluorescent tag on these new contrast agents will enable direct validation of the MRI data with laser scanning confocal microscopy. These data will promote our understanding of the basic mechanisms underlying angiogenesis and resulting image contrast. Its low toxicity, blood vessel specificity and extensive half-life in vivo, could make our lectin-targeted contrast agents an invaluable new tool for monitoring the efficacy of anti-angiogenic therapies in patients. The application titled """"""""A Lectin-Contrast Agent For Multimodality Molecular Imaging of Tumor Angiogenesis"""""""" is centered on developing a novel lectin-based contrast agent for molecular MRI, which preferentially targets blood vessels via the affinity of the lectin from Bandeiraea Simplicifolia for endothelial cells. We intend to synthesize and characterize, both T1 and T2 versions of this contrast agent, and employ them to better understand the role of tumor angiogenesis in a human metastatic breast cancer xenograft model.
|Kim, Eugene; Zhang, Jiangyang; Hong, Karen et al. (2011) Vascular phenotyping of brain tumors using magnetic resonance microscopy (?MRI). J Cereb Blood Flow Metab 31:1623-36|
|Pathak, Arvind P; Penet, Marie-France; Bhujwalla, Zaver M (2010) MR molecular imaging of tumor vasculature and vascular targets. Adv Genet 69:1-30|
|Pathak, Arvind P (2009) Model system takes us a step closer to efficacious imaging biomarkers of angiogenesis in head and neck cancer. Cancer Biol Ther 8:2284-5|