title: Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer.
abstract: Targeted radiopharmaceutical is an effective treatment for solid tumors. By labeling with radionuclides, targeting peptide could achieve both noninvasive diagnosis and targeted radionuclide therapy. In order to evaluate the potential applicability of GEBP11 peptides in diagnosis and radiotherapy of gastric cancer, in this study, iodine 131 labeled GEBP11 peptides, including a novel bifid PEGlylated GEBP11 trimer and its corresponding monomer, were developed. The clinical potential of GEBP11 peptides, such as tumor binding affinity and antitumor efficacy was demonstrated and assessed with multimodality imaging methods. Cerenkov and SPECT imaging showed higher tumor uptake for (131)I-2PEG-(GEBP11)3 (P<0.05, day 1; P<0.01, day 2; vs. monomer). Biodistribution studies indicated higher tumor accumulation and better T/NT of (131)I-2PEG-(GEBP11)3. Bioluminescence imaging exhibited a significant tumor growth suppression in (131)I-2PEG-(GEBP11)3 treated group (P<0.001 vs. control; P<0.01 vs. monomer). After treatment with (131)I-2PEG-(GEBP11)3, the tumor volume and vasculature decreased significantly, and the survival time was prolonged to 75.5days. Meanwhile, no significant hepatic or renal toxicity was observed with (131)I-2PEG-(GEBP11)3 administered. In conclusion, (131)I-2PEG-(GEBP11)3 could be a promising candidate for peptide-based targeting therapy of gastric cancer. 2PEG-(GEBP11)3 might be a potential drug delivery vehicle for the antiangiogenic therapy of gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 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, Xi'an, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: School of Life Science, Dalian Nationalities University, Dalian, China.
authors.forename: Minglei
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 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, Xi'an, China. Electronic address: wangbiaoluodoc@163.com.
authors.forename: Biaoluo
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 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, Xi'an, China. Electronic address: kaicwu228@gmail.com.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China. Electronic address: dingjie@fmmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013270:Stomach / Q000098:blood supply* / Q000473:pathology* / Q000528:radiation effects; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D007457:Iodine Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals
keywords: Gastric cancer; Multimodality imaging; Targeted radionuclide therapy; Trimeric GEBP11 peptide; Tumor vasculature targeting