title: A near-infrared phthalocyanine dye-labeled agent for integrin αvβ6-targeted theranostics of pancreatic cancer.
abstract: Integrin αvβ6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin αvβ6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin αvβ6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. (18)F-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin αvβ6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin αvβ6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer.
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gao
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Chenran
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing 100857, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: liuzf@bjmu.edu.cn.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D004396:Coloring Agents / Q000008:administration & dosage; D064593:Heterografts; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D016023:Integrins / Q000378:metabolism*; D054833:Isoindoles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D000068936:Theranostic Nanomedicine
chemical_list: D000951:Antigens, Neoplasm; D004396:Coloring Agents; D007211:Indoles; D016023:Integrins; D054833:Isoindoles; C073878:integrin alphavbeta6; C013647:phthalocyanine
keywords: Image-guided surgery; Intraoperative imaging; Molecular imaging; Molecular probe; Photodynamic therapy