title: Synthesis and preliminary evaluation of a18F-labeled ethisterone derivative [18F]EAEF for progesterone receptor targeting.
abstract: To develop a novel progesterone receptor-targeting probe for positron emission tomography imaging, an ethisterone derivative [18F]EAEF was designed and prepared in high decay-corrected radiochemical yield (30-35%) with good radiochemical purity (>98%). [18F]EAEF is a lipophilic tracer (logP = 0.53 ± 0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [18F]EAEF were found in uterus (5.73 ± 1.83% ID/g) and ovary (4.05 ± 0.73% ID/g) at 2 hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50 ± 0.17% ID/g). For positron emission tomography imaging, [18F]EAEF showed high uptake in progesterone receptor-positive MCF-7 tumor (3.15 ± 0.07% ID/g at 2 hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7 with EAEF blocking (1.84 ± 0.05% ID/g at 2 hr p.i.) or in progesterone receptor-negative MDA-MB-231 tumor (1.80 ± 0.03% ID/g at 2 hr p.i.). Based on the good stability and specificity of [18F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation.
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Linyi
authors.initials: L
authors.lastname: You
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Mengna
authors.initials: M
authors.lastname: Gao
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Lumei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Rongqiang
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D005003:Ethisterone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D010053:Ovary / Q000378:metabolism; D049268:Positron-Emission Tomography; D066244:Proton Magnetic Resonance Spectroscopy; D011980:Receptors, Progesterone / Q000187:drug effects*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; D011980:Receptors, Progesterone; D005003:Ethisterone
keywords: breast cancer; ethisterone; fluorine-18; positron emission tomography; progesterone receptor