title: An imaging agent to detect androgen receptor and its active splice variants in prostate cancer.
abstract: Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD-targeted (AR LBD-targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V-positive lesions to determine whether they will benefit from further AR LBD-targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR.123I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of123I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC.
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Tien
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Pan
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Jacky K
authors.initials: JK
authors.lastname: Leung
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Banuelos
authors.affiliation: Chemistry and Earth, Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Kunzhong
authors.initials: K
authors.lastname: Jian
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Nasrin R
authors.initials: NR
authors.lastname: Mawji
authors.affiliation: Chemistry and Earth, Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Javier Garcia
authors.initials: JG
authors.lastname: Fernandez
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.affiliation: Chemistry and Earth, Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Andersen
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Marianne D
authors.initials: MD
authors.lastname: Sadar