Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy)ethyl)-5-[^125/131 I]iodo-1,2,3-triazole-diestradiol ([^125/131 I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [^125/131 I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [^125/131 I]ITE2 had good stability in vitro and moderate molar activity (0.3 ± 0.2 GBq/µmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [¹³¹ I]ITE2 had high uptake in ER-abundant uterine and ovarian (5.7 ± 0.4 and 10.1 ± 1.4%ID/g at 1 hr postinjection) and could be blocked by co-injection of estradiol (2.7 ± 0.1 and 5.5 ± 0.4%ID/g) obviously. In the SPECT/CT imaging study, [¹²⁵ I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1 ± 0.4%ID/g) than that of MDA-MB-231 (0.9 ± 0.1%ID/g). Furthermore, the specific uptake of [¹²⁵ I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2 ± 0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis.