title: The feasibility of 18F-AlF-NOTA-PRGD2 PET/CT for monitoring early response of Endostar antiangiogenic therapy in human nasopharyngeal carcinoma xenograft model compared with 18F-FDG.
abstract: OBJECTIVE
  Radiolabeled arginine-glycine-aspartic acid (RGD) peptides have been developed for PET imaging of integrin avβ3 in the tumor vasculature, leading to great potential for noninvasively evaluating tumor angiogenesis and monitoring antiangiogenic treatment. The aim of this study was to investigate a novel one-step labeled integrin-targeted tracer, 18F-AlF-NOTA-PRGD2, for PET/CT for detecting tumor angiogenesis and monitoring the early therapeutic efficacy of antiangiogenic agent Endostar in human nasopharyngeal carcinoma (NPC) xenograft model.
  
  
  RESULTS
  Mice bearing NPC underwent 18F-AlF-NOTA-PRGD2 PET/CT at baseline and after 2, 4, 7, and 14 days of consecutive treatment with Endostar or PBS, compared with 18F-FDG PET/CT. Tumors were harvested at all imaging time points for histopathological analysis with H & E and microvessel density (MVD) and integrin avβ3 immunostaining. The maximum percent injected dose per gram of body weight (%ID/gmax) tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT was significantly lower than that in the control group starting from day 2 (p < 0.01), much earlier and more accurately than that of 18F-FDG PET/CT. Moreover, a moderate linear correlation was observed between tumor MVD and the corresponding tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT (r = 0.853, p < 0.01).
  
  
  CONCLUSIONS
  18F-AlF-NOTA-PRGD2 PET/CT can be used for in vivo angiogenesis imaging and monitoring early response to Endostar antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation.
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.|Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.|Med-X Ruijin Hospital Micro PET/CT Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wangxi
authors.initials: W
authors.lastname: Hai
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Dengbin
authors.initials: D
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016903:Drug Monitoring / Q000379:methods; D043169:Endostatins / Q000627:therapeutic use*; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011994:Recombinant Proteins; D015203:Reproducibility of Results; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C586680:alfatide II; D019788:Fluorodeoxyglucose F18; C522911:endostar protein
keywords: 18F-AlF-NOTA-PRGD2; 18F-FDG; Endostar; NPC; antiangiogenic therapy