title: GX1 targeting delivery of rmhTNFα evaluated using multimodality imaging.
abstract: GX1 is a tumor targeting peptide. In this study, we evaluated the antitumor efficacy of a GX1-derived fusion toxin, GX1-rmhTNFα, and investigated its targeting efficiency and pharmacokinetics in vivo using multimodality imaging. Flow cytometry revealed a greater level of cell apoptosis induced by GX1-rmhTNFα (27.1%) compared with rmhTNFα or a saline control (13.7% and 4.7%, respectively). SPECT (single-photon emission computed tomography) demonstrated high accumulation of GX1-rmhTNFα in tumor site. Biodistribution studies indicated GX1-rmhTNFα was cleared by the liver and kidney, and the drug may not cross the blood-brain barrier. In addition, bioluminescence imaging (BLI) showed that GX1-rmhTNFα caused a satisfactory delay in tumor growth in both subcutaneous and orthotopic cancer models. Contrast-enhanced ultrasound (CEUS) and CD31 staining revealed a loss in blood perfusion and vasculature. TUNEL and Ki67 staining validated the in vivo results. Biochemical analyses revealed limited renal and hepatic toxicity of GX1-rmhTNFα. This study demonstrated that GX1-rmhTNFα is a safe and potent anticancer agent that may have great potential for the targeted therapy of gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Xi'an Children's Hospital, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China.
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China. Electronic address: liangjie@fmmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China. Electronic address: kaicwu228@gmail.com.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods; D010456:Peptides, Cyclic / Q000737:chemistry*; D011993:Recombinant Fusion Proteins; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D010456:Peptides, Cyclic; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C534327:cyclo(cysteinyl-glycyl-aspargyl-seryl-aspargyl-prolyl-lysyl-seryl-cysteine)
keywords: Fusion toxin; Gastric cancer; Molecular imaging; Peptide; Targeted therapy