Wei Wang, PhD University of New Mexico wwang@unm.edu Phone:(505) 277-0756 Personal Website

Title: ICAM-1 Mimics as LFA-1 Inhibitors

Early detection and intervention is one of the most important factors in determining the success rates in the treatment of many types of cancers.  Magnetic resonance imaging (MRI) agents currently used clinically for tumor detection are limited in their ability to target tumor cells, provide high-resolution images, and permeate biological barriers preventing oral administration.  Optical detection technique (e.g., fluorescence) provides high sensitivity, but is limited by optical aberrations and light scattering to an imaging target.  Therefore, new detection agents or probes are urgently needed.  Our research goal is to develop cell permeable, sensitive multimodal fluorescence/MRI probes for tumor imaging that specifically bind to the cell surface monosaccharide sialic acid, which is overexpressed in a number of epithelial-derived cancers.  Our hypothesis is that the significant intrinsic differences in sialic acid expression in tumor cells versus normal cells will result in the preferential targeting of highly sialylated tumor cells by multimodal fluorescence/MRI probes.  With our research experience and results in the development of fluorescence sensors for saccharides, it is possible to design the multimodal MRI/fluorescence chemical probes.  This proposed research will be accomplished by pursuing the following specific aims: Specific Aim 1.  Design, synthesize and test fluorescence probes with high affinity and specificity for sialic acid and sialylated antigens sLex and sLea.  Specific Aim 2.  Design, synthesize and test multimodal fluorescence/MRI probes with high affinity and specificity for sialic acid and sialylated antigens sLex and sLea.  Specific Aim 3.  Evaluate selective targeting efficacy of the multimodal probes using colon COLO-205 cancer cells.  The research results from this proposed study will lay the groundwork for in vivo imaging studies of a variety of tumors.  We believe that the team we have assembled including Professor Larry Sklar as mentor and Professor C. Andy Hu as collaborator for developing these potentially superior probes has the extensive experience and expertise needed to carry out the proposed interdisciplinary research in a timely and successful fashion.