title: Polyethylene glycol (PEG) linked to near infrared (NIR) dyes conjugated to chimeric anti-carcinoembryonic antigen (CEA) antibody enhances imaging of liver metastases in a nude-mouse model of human colon cancer.
abstract: We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases.
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California, United States of America.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Maawy
authors.affiliation: AntiCancer, Inc., San Diego, California, United States of America; Yokohama City University, Yokohama City, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer, Inc., San Diego, California, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: OncoFluor, Inc., San Diego, California, United States of America.
authors.forename: George A
authors.initials: GA
authors.lastname: Luiken
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California, United States of America; AntiCancer, Inc., San Diego, California, United States of America.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California, United States of America; VA San Diego Healthcare System, San Diego, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D059629:Signal-To-Noise Ratio; D051598:Whole Body Imaging
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins; D011092:Polyethylene Glycols