Liu Huanhuan, Lin Xiaoru, Xu Duo, Li Jingchao, Fang Jianyang, Li Jindian, Meng Lingxin, Zeng Xinying, Li Yesen, Huang Jinxiong, Guo Zhide, Zhang Xianzhong
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
The First Affiliated Hospital, Xiamen University, Xiamen 361003, China.
ACS Med Chem Lett. 2022 Jan 27;13(2):203-210. doi: 10.1021/acsmedchemlett.1c00559. eCollection 2022 Feb 10.
Two novel PEGylated ethinylestradiol (PEG = poly(ethylene glycol)) estrogen receptor (ER) targeting probes [I]EITE and [I]MITE were synthesized and evaluated. Both probes had a nanomolar binding affinity to the ER receptor (36.47 nM for [I]EITE and 61.83 nM for [I]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]EITE at 1 h postinjection (p.i.) and to 3.69 for [I]MITE at 2 h p.i. in MCF-7 tumors. Among these two probes, [I]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.
合成并评估了两种新型聚乙二醇化乙炔雌二醇（PEG = 聚乙二醇）雌激素受体（ER）靶向探针[I]EITE和[I]MITE。两种探针均对ER受体具有纳摩尔级的结合亲和力（[I]EITE为36.47 nM，[I]MITE为61.83 nM）。它们在ER阳性MCF-7细胞和肿瘤中摄取率高，预先注射过量雌二醇可显著阻断这种摄取。它们的ER特异性在ER阴性MDA-MB-231细胞和肿瘤摄取率低上进一步得到证明。在MCF-7肿瘤中，注射后1小时[I]EITE的最大肿瘤与肌肉（T/M）比达到6.59，注射后2小时[I]MITE的最大肿瘤与肌肉（T/M）比达到3.69。在这两种探针中，[I]EITE显示出更快的肿瘤蓄积和更高的T/M比，表明它可能是ER阳性乳腺癌潜在诊断的更好候选者。
