Journal of Medicinal Chemistry · 2018 · 20 citations · 24 references
MedicineMolecular BiologyOncologyMolecular ImagingMolecular OncologyNeoplasiaEsophageal CancerLigand BindingLigand-mediated TargetingMolecular Probe DevelopmentTargeted Imaging AgentsTargeting LigandsCancer Targeting LigandsLigand Binding AffinityLigand SelectivityMolecular Targeting LigandsReceptor-targeted Imaging AgentsTargeted Molecular Imaging AgentsTargeting Ligand OptimizationTumor Targeting Ligands
Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells. The Cy5.5-labeled heterodimer QRH*-KSP*-E3-Cy5.5 demonstrated specific binding to each target and showed 3-fold greater fluorescence intensity and 2-fold higher affinity compared with those of either monomer alone. Peak uptake in xenograft tumors was observed at 2 h postinjection with systemic clearance by ∼24 h in vivo. Furthermore, ligand binding was evaluated on human esophageal specimens ex vivo, and 88% sensitivity and 87% specificity were found for the detection of either high-grade dysplasia (HGD) or EAC. This peptide heterodimer shows promise for targeted detection of early Barrett's neoplasia in clinical study.
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Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands
Andreas Becker, Carsten Hessenius, Kai Licha et al. · Nature Biotechnology · 2001 · 520 citations