title: Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer.
abstract: Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and p<0.001 for the 750 dyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the 650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.
authors.affiliation: University of California San Diego, Department of Surgery, 200 West Arbor Drive, No. 8220, San Diego, California 92103-8220.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Maawy
authors.affiliation: University of California San Diego, Department of Surgery, 200 West Arbor Drive, No. 8220, San Diego, California 92103-8220bAntiCancer, Inc., 7917 Ostrow Street, San Diego, California 92111cYokohama City University, Yokohama City 236-0004, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer, Inc., 7917 Ostrow Street, San Diego, California 92111.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: OncoFluor, Inc., 1211 Alameda Boulevard, Coronado, California 92118.
authors.forename: George A
authors.initials: GA
authors.lastname: Luiken
authors.affiliation: University of California San Diego, Department of Surgery, 200 West Arbor Drive, No. 8220, San Diego, California 92103-8220bAntiCancer, Inc., 7917 Ostrow Street, San Diego, California 92111.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: University of California San Diego, Department of Surgery, 200 West Arbor Drive, No. 8220, San Diego, California 92103-8220eVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, California 92161.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins; D011092:Polyethylene Glycols