Poster Sessions

CANCER-11

Celeste Roney

C.A. Roney, B. Xu, J. Xie, G.L. Griffiths, R.M. Summers

Polymerization of Targeted Liposomes for Imaging Colon Polyps in APC Min+/ Mice

Colorectal carcinoma (CRC) is the 2nd leading cause of cancer related deaths in the United States. Mutant adenomatous polyposis coli (APC) genes progress to malignancy if undetected. In vivo detection of polyps improves sensitivity and specificity of diagnosis in non-invasive screening techniques. We have designed liposomal vesicles with incorporated contrast agents, and surface UEA-1 (Ulex europaeus agglutinin) lectin protein receptors that are attracted to the polyps. Lipid films were prepared by mixing the polymerizable phospholipid DAPC with the saturated spacer lipid DMPC or DMPE-GLU in 1:1 ratio together with 1% 18:1 Rhodamine PE. Lipid films were hydrated in 1 mL EtOH and 5 mL Omnipaque iodine contrast solution (350 mgI/mL), and rotavaporized for 2 hrs at 70 °C. A 10 mL LipexTM Thermobarrel Extruder was used to extrude the liposomes in a 60 °C water bath. Liposomes were extruded using 100 nm, 200nm, 400nm and 600nm pore size membranes. A UV Stratalinker 1800® cross-linker was used to polymerize the extruded liposomes for 20 cycles at 3600 µJ per cycle. Freshly excised (N = 6) or mounted (for fluorescent microscopy, N = 13) APC Min+/ specimen were incubated with targeted liposomes (conjugated UEA-1 lectin) or control liposomes (no lectin); Ex vivo imaging techniques were performed by multispectral optical imaging (see Fig. 1) and microCT. CT Hounsfield unit quantitative analyses show targeted liposomes more strongly bind polyps (312.83 ± 6.81 HU versus normal tissue, 25.67 ± 11.24 HU) than do nontargeted liposomes (170.1 ± 8.49 HU versus normal mucosa 9.03 ± 6.22 HU). Since UEA-1 lectin specifies α-L-fucose carbohydrate expression of the mucin glycoprotein layer of the polyps, opportunities abound for improved sensitivity and specificity of diagnostic accuracy in CRC detection. Results of imaging experiments will be presented.