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.
Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear, Instituto Superior Técnico, Universidade Técnica de Lisboa, Estrada Nacional 10, 2686-953 Sacavém, Portugal.
Carina
C
Neto
Maria Cristina
MC
Oliveira
Lurdes
L
Gano
Fernanda
F
Marques
Takumi
T
Yasuda
Thies
T
Thiemann
Torsten
T
Kniess
Isabel
I
Santos
D001943:Breast Neoplasms / Q000175:diagnosis*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D047628:Estrogen Receptor alpha / Q000737:chemistry*; D005260:Female; D005461:Fluorine; D006801:Humans; D007455:Iodine; D009682:Magnetic Resonance Spectroscopy; D009376:Neoplasms, Hormone-Dependent / Q000175:diagnosis*; D049268:Positron-Emission Tomography; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D015899:Tomography, Emission-Computed, Single-Photon
D047628:Estrogen Receptor alpha; D011994:Recombinant Proteins; D005461:Fluorine; D004958:Estradiol; D007455:Iodine