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

To develop potential radiolabelled probes for SPECT/PET imaging estrogen receptor (ER) positive tumors, 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-compounds, 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%) among the halophenylethynyl compounds studied and should be further explored as potential PET biomarkers for imaging of ER expressing tumors.