title: BODIPY-17α-ethynylestradiol conjugates: Synthesis, fluorescence properties and receptor binding affinities.
abstract: In vivo imaging of estrogen receptor (ER) densities in human breast cancer is a potential tool to stage disease, guide treatment protocols and follow-up on treatment outcome. Both positron emission tomography (PET) and fluorescence imaging have received ample attention to detect ligand-ER interaction. In this study we prepared BODIPY-estradiol conjugates using 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as fluorescent probe and estradiol derivatives as ligand and established their relative binding affinity (RBA) for the ERα. The synthesis of the conjugates involves attachment of a BODIPY moiety to the C17α-position of estradiol using Sonogashira or click reactions of iodo-BODIPY or aza-BODIPY with various 17α-ethynylestradiol (EE2) derivatives. The highest RBA for the ERα was observed with the EE2-BODIPY conjugate (7) featuring a linear eight carbon spacer chain. Cell uptake studies and in vivo imaging experiments in an ER-positive mouse tumor model are in progress.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Osati
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Hasrat
authors.initials: H
authors.lastname: Ali
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Paquette
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Beaudoin
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada; Centre d'Imagerie Moléculaire de l'Université de Sherbrooke (CIMUS), CR-CHUS, 3001 12(e) Avenue Nord, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guerin
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada; Centre d'Imagerie Moléculaire de l'Université de Sherbrooke (CIMUS), CR-CHUS, 3001 12(e) Avenue Nord, Sherbrooke, Québec J1H5N4, Canada.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Leyton
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec J1H5N4, Canada; Centre d'Imagerie Moléculaire de l'Université de Sherbrooke (CIMUS), CR-CHUS, 3001 12(e) Avenue Nord, Sherbrooke, Québec J1H5N4, Canada. Electronic address: Johan.E.vanlier@usherbrooke.ca.
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
mesh_terms: D001896:Boron Compounds / Q000737:chemistry*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D057930:Click Chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000737:chemistry*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D049268:Positron-Emission Tomography; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D003287:Contrast Media; D047628:Estrogen Receptor alpha; D004997:Ethinyl Estradiol
keywords: 17α-Ethynylestradiol conjugates; BODIPY; Estrogen receptor; Fluorescence imaging; RBA