State Key Laboratory of Molecular Vaccinology and Molecular, Diahgnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.
Chem Biol Drug Des. 2020 Dec;96(6):1332-1340. doi: 10.1111/cbdd.13754. Epub 2020 Aug 19.
The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy)ethyl)-5-[ I]iodo-1,2,3-triazole-diestradiol ([ I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [ I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [ 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 [ 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, [ 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 [ 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.
本研究旨在开发一种 1-(2-(2-(2-(1,2,3-三唑)乙氧基)乙氧基)乙基)-5-[I]碘-1,2,3-三唑-二雌二醇([I]ITE2)，用于雌激素受体(ER)表达的乳腺癌单光子发射计算机断层扫描(SPECT)成像。[I]ITE2 的放射化学产率（94.4±0.4%）高，放射化学纯度（>99%）高。[I]ITE2 在体外稳定性好，摩尔活度适中（0.3±0.2GBq/µmol）。在所有时间点，ER 阳性 MCF-7 细胞的摄取均高于 ER 阴性 MDA-MB-231 细胞。大鼠生物分布显示，[I]ITE2 在富含 ER 的子宫和卵巢中的摄取率较高（注射后 1 小时分别为 5.7±0.4%和 10.1±1.4%ID/g），并且可以通过与雌二醇共注射明显阻断（2.7±0.1%和 5.5±0.4%ID/g）。在 SPECT/CT 成像研究中，[I]ITE2 在 MCF-7 肿瘤（3.1±0.4%ID/g）中的摄取明显高于 MDA-MB-231（0.9±0.1%ID/g）。此外，预先给予氟维司群可有效阻断[I]ITE2 在 ER 阳性 MCF-7 肿瘤中的特异性摄取（1.2±0.4%ID/g）。设计并合成了一种新型放射性碘标记的二聚雌激素，具有良好的 ER 靶向能力和特异性。进一步验证该二聚体在 ER 阳性乳腺癌诊断中的优势是值得的。
