title: PEGylation enhances the tumor selectivity of melanoma-targeted conjugates.
abstract: In the development of our melanoma-selective delivery approach, three preselected conjugates of 5-iodo-2'-deoxyuridine (IUdR) to the ICF01012 melanoma-carrier were radiolabelled with iodine-125, and their in vivo distribution profile was determined. A radioiodination method for the conjugate 1a and its PEGylated derivatives 1b-c was developed via electrophilic iododestannylation in good radiochemical yield with excellent radiochemical purity (>99%). When administered to melanoma-bearing mice, the PEGylated conjugates exhibited an increased tumour uptake with a prolonged residence time. PEGylation also resulted in enhanced tumour selectivity compared with the non-PEGylated parent. These characteristics support further development of this model to achieve maximal concentration of anticancer therapeutics at the local site of action and minimize distribution to non-targeted sites.
authors.affiliation: INSERM - Université d'Auvergne UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France. emmanuelle.mounetou@inserm.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: André
authors.forename: Sophie
authors.initials: S
authors.lastname: Besse
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mounetou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols