title: Radioiodination of glycoprotein-conjugated liposomes by using the Bolton-Hunter reagent and biodistribution in tumor-bearing mice.
abstract: We have developed a suitable radiolabeling method for our new type of glycoprotein-liposome conjugate (GCL), in order to investigate its potential utility as a drug carrier that can target the cellular functions of carbohydrate-binding proteins. In order to obtain radiolabeled GCL with high labeling efficiency, we introduced p-hydroxyphenylpropyl groups into the liposome membrane through the amine moiety of a constitutive phospholipid, dipalmitoylphosphatidylethanolamine (DPPE) by using Bolton-Hunter reagent (BHR). Radioiodination of the introduced tyrosyl groups was performed by the Chloramine-T method. The labeling efficiency of the BHR-treated liposome conjugate was high in comparison with that of the BHR-untreated liposome conjugate. An in vitro inhibition study showed that the binding affinity of 125I-labeled BHR-treated GCL (125I-F3S-BH) with lectin was twice as high as that of untreated conjugate (125I-F3S). The biodistribution of 125I-F3S-BH in mice was considerably different from that of 125I-F3S. 125I-F3S-BH was more rapidly taken up by the liver and was more rapidly excreted from the liver than 125I-F3S. Moreover, 125I-F3S-BH accumulated more rapidly into the kidneys, which resulted a lower radioactivity in the blood circulation at an earlier time point than in the case of 125I-F3S. The characteristics of tumor accumulation of 125I-F3S-BH and 125I-F3S were similar to those in blood. If F3S is to be employed as an in vivo targeting ligand in biodistribution studies, BHR would be a suitable tool for radiolabeling because it allows GCL to retain the biological activity and characteristics of the unmodified conjugate.
authors.affiliation: Faculty of Pharmaceutical Sciences, Science University of Tokyo, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shimura
authors.forename: Y
authors.initials: Y
authors.lastname: Sogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakita
authors.forename: M
authors.initials: M
authors.lastname: Ikekita
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
authors.forename: S
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging / Q000378:metabolism*; D002700:Chloramines / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013388:Succinimides / Q000737:chemistry*; D014018:Tissue Distribution; D014105:Tosyl Compounds / Q000737:chemistry*; D000509:alpha-Fetoproteins / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D002700:Chloramines; D004337:Drug Carriers; D008081:Liposomes; D019275:Radiopharmaceuticals; D013388:Succinimides; D014105:Tosyl Compounds; D000509:alpha-Fetoproteins; C016300:chloramine-T; C022581:Bolton-Hunter reagent