title: Synthesis of IR-780 dye-conjugated abiraterone for prostate cancer imaging and therapy.
abstract: Near-infrared fluorescence (NIRF) imaging is a novel imaging modality that allows for detection and real‑time monitoring of various pathophysiological states. IR-780 iodide has been used as an ideal platform to construct theranostic agents for cancer imaging and therapy. Abiraterone is a 17α‑hydroxylase/C17, 20‑lyase (CYP17) inhibitor that has been approved for use in patients with prostate cancer after androgen deprivation therapy. We report the synthesis and characterization of IR-780 conjugated abiraterone for the dual purpose of prostate cancer imaging and therapy. The new compound Abi-780 retained the excellent photophysical characteristics and NIRF imaging property of IR-780 dye. Abi-780 preferentially accumulated in plasmonic organelles of prostate cancer cells but not in normal prostate epithelial cells. Dose-dependent inhibition of cultured prostate cancer cells by Abi-780 was found. Abi-780 at 20 µM significantly reduced the capabilities of colony formation and migration/invasion potential as well as increasing the apoptosis rate of prostate cancer cells. NIRF imaging using Abi-780 selectively identified the tumors in mice bearing prostate cancer xenografts. Moreover, Abi-780 treatment significantly retarded the tumor growth. No severe systemic toxicity was observed in mice with daily injection of high-dose Abi-780 for one month. In conclusion, biocompatible Abi-780 is highly effective both in prostate cancer imaging and therapy. Constructing theranostic agents using the NIRF dye platform holds great promise in accurate diagnosis and targeted treatment of cancer.
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Gene Technology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Zifan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Ronald Reagan UCLA Medical Center, UCLA Medical Center, Santa Monica, CA, USA.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, University of California at Davis Cancer Center, Sacramento, CA, USA.
authors.forename: Chongxian
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Wanxiang
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Keke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000736:Androstenes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D000736:Androstenes; D005456:Fluorescent Dyes; D007211:Indoles; C089740:abiraterone