Radioiodinated Ethinylestradiol Derivatives for Estrogen Receptor Targeting Breast Cancer Imaging.

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.