Radioiodinated Ethinylestradiol Derivatives for Estrogen Receptor Targeting Breast Cancer Imaging
Radioiodinated Ethinylestradiol Derivatives for Estrogen Receptor Targeting Breast Cancer Imaging
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用于靶向乳腺癌成像的雌激素受体的放射性碘化炔雌醇衍生物
DOI：
10.1021/acsmedchemlett.1c00559
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发表时间：
2022-02-10
影响因子：
4.2
通讯作者：
Zhang, Xianzhong
中科院分区：
文献类型：
--
作者：
Liu, Huanhuan;Lin, Xiaoru;Zhang, Xianzhong
合成并评价了两种新型聚乙二醇化炔雌醇雌激素受体（ER）靶向探针[I-131]EITE和[I-131]MITE。两种探针对ER受体的结合亲和力均为纳米摩尔（[I-131]EITE为36.47 nM， [I-131]MITE为61.83 nM）。它们在er阳性MCF-7细胞和肿瘤中表现出高摄取，这可以通过联合注射过量的雌二醇来显着阻断。在ER阴性的MDA-MB-231细胞和肿瘤中的低摄取进一步证明了它们的ER特异性。在MCF-7肿瘤中，注射后1小时[I-131]EITE的最大肿瘤与肌肉（T/M）比达到6.59，注射后2小时[I-131]MITE的最大肿瘤与肌肉（T/M）比达到3.69。在这两种探针中，[I-131]EITE显示出更快的肿瘤积累和更高的T/M比，这表明它可能是更好的潜在诊断er阳性乳腺癌的候选物。
Two novel PEGylated ethinylestradiol (PEG = poly(ethylene glycol)) estrogen receptor (ER) targeting probes [I-131]EITE and [I-131]MITE were synthesized and evaluated. Both probes had a nanomolar binding affinity to the ER receptor (36.47 nM for [I-131]EITE and 61.83 nM for [I-131]MITE). They showed high uptake in ER-positive MCF-7 cells and tumors, which could be significantly blocked by a coinjection of excess estradiol. Their ER specificities were further demonstrated by the low uptake in ER negative MDA-MB-231 cells and tumors. The maximum tumor-to-muscle (T/M) ratios reach to 6.59 for [I-131]EITE at 1 h postinjection (p.i.) and to 3.69 for [I-131]MITE at 2 h p.i. in MCF-7 tumors. Among these two probes, [I-131]EITE showed a faster tumor accumulation and a higher T/M ratio indicating it could be a better candidate for the potential diagnosis of ER-positive breast cancers.