Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography.
Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography.
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DOI：
10.1158/0008-5472.can-09-4396
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发表时间：
2010-05-15
期刊：
影响因子：
11.2
通讯作者：
Pomper MG
中科院分区：
文献类型：
--
作者：
Nimmagadda S;Pullambhatla M;Stone K;Green G;Bhujwalla ZM;Pomper MG
趋化因子受体CXCR4及其同源配体CXCL12对许多肿瘤类型发生转移至关重要。因此，CXCR4可能为转移的分子成像提供一个细胞表面靶点，有助于诊断、分期和治疗监测。此外，对原发肿瘤CXCR4状态的无创检测可能为病变的转移潜能提供一个指标。在此，我们报道了干细胞动员剂普乐沙福的一种正电子发射类似物[64Cu]AMD3100的研发和评估，用于对预先选择的具有不同CXCR4表达水平的人肿瘤异种移植物中的该受体进行成像。这种成像方法也在源自人MDA - MB - 231乳腺癌细胞的肺转移中进行了评估。为验证体内成像数据而进行的体外生物分布研究证实了[64Cu]AMD3100对CXCR4表达进行成像的能力。我们的研究结果证明了使用一种临床批准的药物作为分子支架，通过正电子发射断层扫描（PET）对CXCR4进行无创成像的可行性。
The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging and therapeutic monitoring. Further, Noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of a positron-emitting analog of the stem cell mobilizing agent plerixafor, [64Cu]AMD3100, to image this receptor in human tumor xenografts preselected for graded expression of CXCR4. This imaging method was also evaluated in a lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [64Cu]AMD3100 to image CXCR4 expression. Our findings demonstrate the feasibility of noninvasively imaging CXCR4 by positron emission tomography (PET) using a clinically approved agent as a molecular scaffold.