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Mol Pharm. 2011 Dec 5;8(6):2444-53. doi: 10.1021/mp200401p. Epub 2011 Nov 15.

Hybrid peptide dendrimers for imaging of chemokine receptor 4 (CXCR4) expression.

Author information

1
Division of Diagnostic Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.

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.

PMID:
22085282
PMCID:
PMC3711081
DOI:
10.1021/mp200401p
[Indexed for MEDLINE]
Free PMC Article

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