title: Synthesis and Biological Evaluation of New Quinoxaline Derivatives of ICF01012 as Melanoma-Targeting Probes.
abstract: The aim of this study was the synthesis and pharmacokinetic selection of a best melanin-targeting ligand for addressing anticancer agents to pigmented melanoma. Seven quinoxaline carboxamide derivatives were synthesized and radiolabeled with iodine-125. Biodistribution studies of compounds [ (125) I]1a-g performed in melanoma-bearing mice tumor showed significant tumor uptake (range 2.43-5.68%ID/g) within 1 h after i.v. injection. Fast clearance of the radioactivity from the nontarget organs mainly via the urinary system gave high tumor-to-blood and tumor-to-muscle ratios. Given its favorable clearance and high tumor-melanoma uptake at 72 h, amide 1d was the most promising melanoma-targeting ligand in this series. Compound 1d will be used as building block for the design of new melanoma-selective drug delivery systems.
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Radhia
authors.initials: R
authors.lastname: El Aissi
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Liu
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Besse
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Canitrot
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chavignon
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.affiliation: INSERM-Université d'Auvergne , UMR 990, IMTV, BP 184, F-63005 Clermont-Ferrand Cedex, France ; Clermont Université , Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63005 Clermont-Ferrand Cedex, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Moreau
keywords: Melanoma; iodine-125; melanin-targeting ligand; radiolabeling