title: Hybrid peptide dendrimers for imaging of chemokine receptor 4 (CXCR4) expression.
abstract: The chemokine receptor 4 (CXCR4), which is overexpressed in many types of cancer, is an emerging target in the field of molecular imaging and therapeutics. The CXCR4 binding of several peptides, including the cyclic Ac-TZ14011, has already been validated. In this study mono-, di- and tetrameric Ac-TZ14011-containing dendrimers were prepared and functionalized with a multimodal (hybrid) label, consisting of a Cy5.5-like fluorophore and a DTPA chelate. Confocal microscopy revealed that all three dendrimers were membrane bound at 4 °C, consistent with CXCR4 binding in vitro. The unlabeled dimer and tetramer had a somewhat lower affinity for CXCR4 than the unlabeled monomer. However, when labeled with the multimodal label the CXCR4 affinity of the dimer and tetramer was considerably higher compared to that of the labeled monomer. On top of that, biodistribution studies revealed that the additional peptides in the dimer and tetramer reduced nonspecific muscle uptake. Thus, multimerization of the cyclic Ac-TZ14011 peptide reduces the negative influence of the multimodal label on the receptor affinity and the biodistribution.
authors.affiliation: Division of Diagnostic Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.
authors.forename: Joeri
authors.initials: J
authors.lastname: Kuil
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.forename: Joppe
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D003952:Diagnostic Imaging; D019281:Dimerization; D005456:Fluorescent Dyes / Q000737:chemistry; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D018613:Microscopy, Confocal; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D050091:Dendrimers; D005456:Fluorescent Dyes; D010455:Peptides; D019718:Receptors, CXCR4
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