64Cu-AMD3100——一种用于靶向趋化因子受体CXCR4的新型成像剂。
64Cu-AMD3100--a novel imaging agent for targeting chemokine receptor CXCR4.
作者信息
Jacobson Orit, Weiss Ido D, Szajek Lawrence, Farber Joshua M, Kiesewetter Dale O
机构信息
Positron Emission Tomography Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD 20892, USA.
出版信息
Bioorg Med Chem. 2009 Feb 15;17(4):1486-93. doi: 10.1016/j.bmc.2009.01.014. Epub 2009 Jan 15.
Abstract
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 (64)Cu-AMD3100 with a specific activity of 11.28Ci/ micromol (417GBq/ micromol) 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. (64)Cu-AMD3100 binding affinity to CXCR4 was found to be 62.7 microM. Biodistribution of (64)Cu-AMD3100 showed accumulation in CXCR4-expressing organs and tissues, a renal clearance pathway, and an anomalous specific accumulation in the liver. We conclude that (64)Cu-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.
摘要
CXCR4是一种趋化因子受体，已被证明多种肿瘤利用它来提高生存率、侵袭能力并归巢至靶器官。我们开发了一种一步法放射性合成方法，用铜-64标记CXCR4特异性拮抗剂AMD3100，在放射性合成结束时产生比活度为11.28Ci/微摩尔（417GBq/微摩尔）的（64）Cu-AMD3100。将铜（II）离子掺入AMD3100中并没有改变其抑制细胞对（唯一的）CXCR4配体SDF-1/CXCL12作出反应而发生迁移的能力。发现（64）Cu-AMD3100与CXCR4的结合亲和力为62.7微摩尔。（64）Cu-AMD3100的生物分布显示在表达CXCR4的器官和组织中蓄积，存在肾脏清除途径，并且在肝脏中存在异常的特异性蓄积。我们得出结论，（64）Cu-AMD3100作为一种潜在的PET成像剂，在可视化CXCR4阳性肿瘤和转移灶方面显示出前景，并且可能用于指导和监测抗CXCR4肿瘤治疗。
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