In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer.
In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer.
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DOI：
10.1158/0008-5472.can-11-1226
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Degani H
中科院分区：
文献类型：
--
作者：
Pais A;Gunanathan C;Margalit R;Biton IE;Yosepovich A;Milstein D;Degani H
雌激素受体α（ER）的组织学过表达是乳腺癌中公认的预后标志物。可以检测ER过表达的非侵入性成像技术将在患者活检难以获得的各种情况下有用。本研究的重点是通过体内磁共振成像（MRI）策略来测量人类乳腺癌原位小鼠模型中ER表达水平。具体而言，在ER阳性或ER阴性肿瘤中检查了基于吡啶-四乙酸盐-Gd（III）螯合物（PTA-Gd）与17β-雌二醇（EPTA-Gd）或他莫昔芬（TPTA-Gd）偶联的新型ER靶向造影剂。EPTA-Gd与ER的特异性相互作用的检测被证明可以区分ER阳性和ER阴性肿瘤。体内竞争实验证实EPTA-Gd的增强的检测能力是基于特异性的ER靶向。相比之下，PTA-Gd作为细胞外探针，在任一肿瘤类型中类似地增强ER检测，证实了模型中ER阳性和阴性肿瘤中类似的血管灌注效率。最后，TPTA-Gd选择性地在肌肉中积累，不能优先识别ER阳性肿瘤。总之，这些结果定义了一种新的MRI探头，可以允许ER阳性肿瘤在体内的选择性非侵入性成像。
Histological overexpression of the estrogen receptor α (ER) is a well established prognostic marker in breast cancer. Non-invasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patient's biopsies are problematic to obtain. This study focused on developing by in vivo magnetic resonance imaging (MRI) strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA-Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and negative tumors in the model. Lastly, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo.