Positron Emission Tomography Imaging of Tumors Expressing the Human Chemokine Receptor CXCR4 in Mice with the Use of 64Cu-AMD3100

被引：43

作者：

Weiss, Ido D. ^{[1
]}

Jacobson, Orit ^{[2
]}

Kiesewetter, Dale O. ^{[2
]}

Jacobus, John P. ^{[3
]}

Szajek, Lawrence P. ^{[4
]}

Chen, Xiaoyuan ^{[2
]}

Farber, Joshua M. ^{[1
]}

机构：

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

[2] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, Bethesda, MD 20892 USA

[3] NIH, Radiat Safety Operat Branch, Bethesda, MD 20892 USA

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

来源：

MOLECULAR IMAGING AND BIOLOGY | 2012年 / 14卷 / 01期

关键词：

CXCR4; AMD3100; PET; Tumor; Imaging; CANCER METASTASIS; FACTOR-I; CELLS; MICROENVIRONMENT; REPLICATION; XENOGRAFTS; INHIBITION; ANTAGONIST; SYSTEM; GROWTH;

D O I：

10.1007/s11307-010-0466-y

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Purpose: Expression of CXCR4 in cancers has been correlated with poor prognosis and increased metastasis. Quantifying CXCR4 expression non-invasively might aid in prognostication and monitoring therapy. We evaluated a radiolabeled antagonist of CXCR4, Cu-64-AMD3100, as a positron-emitting imaging agent. Procedures: CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of Cu-64-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays. Results: Cu-64-AMD3100 accumulated in CXCR4-expressing, but not CXCR4-negative, tumors. For CXCR4-expressing tumors, tumor-to-blood and tumor-to-muscle ratios were 23-41 and 50-59, respectively, depending on tumor type. Excess of unlabeled Cu-AMD3100 or AMD3100 significantly reduced Cu-64-AMD3100 accumulation in CXCR4-expressing tumors. Human-absorbed dose calculations predicted a dose limit of 444 MBq. Conclusions: CXCR4 can be imaged in tumors using Cu-64-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that Cu-64-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.

引用

页码：106 / 114

页数：9

共 38 条

[1] CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy [J].