title: SPECT imaging of interleukin-6 receptor in ovarian tumor xenografts with a novel radiotracer of 99mTc-HYNIC-Aca-LSLITRL.
abstract: Growing evidences have shown that the IL-6/IL-6R signal pathway promotes the tumor growth, angiogenesis, invasion and migration in various cancers, especially for epithelial ovarian cancer. Hence, including anti-IL-6 antibody (Siltuximab) and anti-IL-6R antibody (Tocilizumab), more and more therapeutic drugs targeting IL-6/IL-6R pathway were developed to block their activity. The molecular imaging of IL-6R is a significant factor for predicting tumor response to IL-6/IL-6R targeted drugs. However, few probes targeting IL-6R were designed and used for the specific detection. The purpose of this study was to develop and evaluate a novel radiotracer, (99m)Tc-HYNIC-Aca-LSLITRL, for SPECT imaging of interleukin-6 receptor. The expression of IL-6R was determined by western blot, immunofluorescence and immunohistochemistry. HYNIC-Aca-LSLITRL and HYNIC-Aca-TLQASIL were synthesized, and then were labeled with 99mTc. The stability and the cell-binding assay were performed. Ovarian tumor xenografts were established and subjected to SPECT imaging after injection of these two radiopharmaceuticals with or without excess primary peptides. The biodistribution of these two radiotracers was performed in nude mice bearing C13K tumors. (99m)Tc-HYNIC-Aca-LSLITRL and (99m)Tc-HYNIC-Aca-TLQASIL were obtained in >95 % labeling yield with favorably stability. In vitro studies demonstrated that the interleukin-6 receptor was overexpressed in ovarian cancer C13K cells. The SPECT imaging of interleukin-6 receptor and biodistribution studies showed that (99m)Tc-HYNIC-Aca-LSLITRL had higher tumor uptake and significantly lower kidney accumulation compared to (99m)Tc-HYNIC-Aca-TLQASIL. (99m)Tc-HYNIC-Aca-LSLITRL could be a promising agent for SPECT imaging of interleukin-6 receptor of ovarian cancer especially for those anti-IL-6R drugs under clinical trials, such as tocilizumab.
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wei
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Mengqin
authors.initials: M
authors.lastname: Lv
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xi
authors.affiliation: Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China. aiyi_aiyi@163.com.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People's Republic of China. doctormxy@126.com.
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015850:Interleukin-6; D015609:Organotechnetium Compounds; D010455:Peptides; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D019947:Receptors, Interleukin-6
keywords: 99mTc-HYNIC-Aca-LSLITRL; 99mTc-HYNIC-Aca-TLQASIL; Interleukin-6 receptor; Molecular imaging; Ovarian cancer