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Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7.

Abstract：

:The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye(®)800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1-92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature.

journal_name

Clin Exp Metastasis

journal_title

Clinical & experimental metastasis

authors

Meincke M,Tiwari S,Hattermann K,Kalthoff H,Mentlein R

doi

10.1007/s10585-011-9403-y

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

713-20

issue

8

eissn

0262-0898

issn

1573-7276

journal_volume

28

pub_type

杂志文章

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