64Cu-AMD3100-A novel imaging agent for targeting chemokine receptor CXCR4

被引：107

作者：

Jacobson, Orit ^{[1
]}

Weiss, Ido D. ^{[2
]}

Szajek, Lawrence ^{[3
]}

Farber, Joshua M. ^{[2
]}

Kiesewetter, Dale O. ^{[1
]}

机构：

[1] Natl Inst Biomed Imaging & Bioengn, Positron Emiss Tomog Radiochem Grp, Bethesda, MD 20892 USA

[2] NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA

[3] NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 04期

关键词：

AMD3100; CXCR4; PET; Copper-64; IN-VIVO BEHAVIOR; HUMAN-IMMUNODEFICIENCY-VIRUS; PROSTATE-CANCER METASTASIS; BIS-TETRAAZAMACROCYCLES; PROTECTING GROUPS; AROMATIC LINKER; BREAST-CANCER; TUMOR-GROWTH; CELLS; EXPRESSION;

D O I：

10.1016/j.bmc.2009.01.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

CXCR4 is a chemokine receptor which has been shown to be exploited by various tumors for increased survival, invasion, and homing to target organs. We developed a one step radiosynthesis for labeling the CXCR4-specific antagonist AMD3100 with Cu-64 to produce Cu-64-AMD3100 with a specific activity of 11.28 Ci/mu mol (417 GBq/mu mol) at the end of radiosynthesis. Incorporation of Cu(II) ion into AMD3100 did not change its ability to inhibit cellular migration in response to the (only) CXCR4 ligand, SDF-1/CXCL12. Cu-64-AMD3100 binding affinity to CXCR4 was found to be 62.7 mu M. Biodistribution of Cu-64-AMD3100 showed accumulation in CXCR4-expressing organs and tissues, a renal clearance pathway, and an anomalous specific accumulation in the liver. We conclude that Cu-64-AMD3100 exhibits promise as a potential PET imaging agent for visualization of CXCR4-positive tumors and metastases and might be used to guide and monitor anti-CXCR4 tumor therapy. (c) Published by Elsevier Ltd.

引用

页码：1486 / 1493

页数：8

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