新型 7α-烷氧基-17α-(4'-卤代苯乙炔基)雌二醇作为表达雌激素受体的肿瘤的 SPECT/PET 成像剂：合成与结合亲和力评价。

Novel 7α-alkoxy-17α-(4'-halophenylethynyl)estradiols as potential SPECT/PET imaging agents for estrogen receptor expressing tumours: synthesis and binding affinity evaluation.

机构信息

Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear, Instituto Superior Técnico, Universidade Técnica de Lisboa, Estrada Nacional 10, 2686-953 Sacavém, Portugal.

出版信息

Steroids. 2012 Sep;77(11):1123-32. doi: 10.1016/j.steroids.2012.05.004. Epub 2012 May 24.

DOI:10.1016/j.steroids.2012.05.004

PMID:22633985

Abstract

In order to develop potential radiolabelled probes for imaging estrogen receptor (ER) positive tumours, we have synthesized and characterized a series of novel 7α-alkoxy-17α-(4'-iodophenylethynyl)estra-1,3,5(10)-triene-3,17β-diols and 7α-alkoxy-17α-(4'-fluorophenylethynyl)estra-1,3,5(10)-triene-3,17β-diols. The fluoro-substituted compounds showed a higher ER binding affinity than the corresponding iodo-derivatives, where 7α-methoxy- and 17α-(4'-fluorophenylethynyl)estra-1,3,5(10)-triene-3,17β-diol showed the highest ER binding affinities (RBA=80.9% and 78.9%, respectively), among the halophenylethynyl compounds studied and should be further explored as potential PET biomarkers for imaging of ER expressing tumours.

摘要

为了开发用于成像雌激素受体（ER）阳性肿瘤的潜在放射性标记探针，我们合成并表征了一系列新型 7α-烷氧基-17α-（4′-碘苯乙炔基）雌-1,3,5(10)-三烯-3,17β-二醇和 7α-烷氧基-17α-（4′-氟苯乙炔基）雌-1,3,5(10)-三烯-3,17β-二醇。氟取代化合物比相应的碘代衍生物具有更高的 ER 结合亲和力，其中 7α-甲氧基和 17α-（4′-氟苯乙炔基）雌-1,3,5(10)-三烯-3,17β-二醇表现出最高的 ER 结合亲和力（RBA=80.9%和 78.9%，分别），在研究的卤代苯乙炔基化合物中，它们应该作为潜在的 PET 生物标志物进一步探索，用于成像 ER 表达的肿瘤。