Synthesis and Biological Evaluation of New Quinoxaline Derivatives of ICF01012 as Melanoma-Targeting Probes AissiRadhia El LiuJianrong BesseSophie CanitrotDamien ChavignonOlivier ChezalJean-Michel Miot-NoiraultElisabeth MoreauEmmanuel 2014 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 <b>[</b><sup><b>125</b></sup><b>I]­1a–g</b> 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 <b>1d</b> was the most promising melanoma-targeting ligand in this series. Compound <b>1d</b> will be used as building block for the design of new melanoma-selective drug delivery systems.