Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

Abstract

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 ERabundant 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.

Synthesis, stability, and cellular uptake of 131I-estradiol against MCF7 and T-47D human cell lines as a radioligand for binding assay

“…Estradiol is a compound that can be easily to radiolabel and developed using 125/131 Iodine or Tritium ( 3 H) [ 15 ]. This radioligand is paired with ER and must be compatible and have the same action or agonist with the receptor [ 16 ].…”

“…Xu et al. have developed a radioiodinated 125/131 I-estradiol dimer for estrogen receptor-targeted breast cancer imaging [ 16 ]. Indirect labeling of β-estradiol-17β-hemisuccinate using histamine with 125 I conducted by Susilo et al.…”