title: Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in the APC(Min/+) mouse using optical colonography.
abstract: Mutated adenomatous polyposis coli (APC) genes predispose transformations to neoplasia, progressing to colorectal carcinoma. Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents were fabricated to locate and image adenomatous polyps in APC(Min/+) mice. The biomarker α-L-fucose covalently joins the liposomal conjugated lectin Ulexeuropaeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (rhodamine B 532 nm emission, 590-620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4-fold labeling efficiency. High-resolution coregistered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal the spatial correlation of contrast distribution and tissue morphology. Freshly excised APC(Min) bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or iohexol (Omnipaque) and imaged by the three techniques. Computed tomographic quantitative analyses did not confirm that targeted liposomes more strongly bound polyps than nontargeted liposomes or iohexol (Omnipaque) alone. OCT, with anatomic depth capabilities, along with the coregistered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes α-l-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APC(Min) mice.
authors.affiliation: Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences Department, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1182, USA.
authors.forename: Celeste A
authors.initials: CA
authors.lastname: Roney
authors.forename: Biying
authors.initials: B
authors.lastname: Xu
authors.forename: Jianwu
authors.initials: J
authors.lastname: Xie
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Wierwille
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Gary L
authors.initials: GL
authors.lastname: Griffiths
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Summers
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D018256:Adenomatous Polyps / Q000473:pathology*; D000818:Animals; D003106:Colon / Q000378:metabolism / Q000473:pathology; D023881:Colonography, Computed Tomographic / Q000379:methods*; D015179:Colorectal Neoplasms / Q000473:pathology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D037121:Plant Lectins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D008081:Liposomes; D037121:Plant Lectins; C036850:Ulex europaeus lectins