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

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.

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► Development of potential probes for estrogen receptor imaging.
► Synthesis of novel 7α-alkoxy-17α-(4′-halophenylethynyl)estradiols.
► Efficient use of Sonogashira reaction for preparation of 4′-halophenyl derivatives.
► Competitive binding assays show high affinity for 4′-fluorophenyl derivatives.