title: MicroPET imaging of tumor angiogenesis and monitoring on antiangiogenic therapy with an (18)F labeled RGD-based probe in SKOV-3 xenograft-bearing mice.
abstract: So far, there is no satisfactory imaging modality to monitor antiangiogenesis therapy of ovarian cancer noninvasively. The aim of this study was to evaluate the effectiveness and sensibility of an (18)F labeled Arg-Gly-Asp (RGD) peptide in imaging and monitoring antiangiogenic responds in SKOV-3 xenograft-bearing mice. (18)F-FB-NH-PEG4-E[PEG4-c(RGDfK)]2 (denoted as (18)F-RGD2) was synthesized and employed in this study. Mice bearing ovarian cancer SKOV-3 tumors were used for biodistribution and microPET imaging studies compared with (18)F-FDG imaging. Animals were treated with low-dose paclitaxel and the effect of paclitaxel therapy on (18)F-RGD2 accumulation was investigated. Microvascular density (MVD) of SKOV-3 tumors was detected to assess the reliability of (18)F-RGD2 in antiangiogenesis monitoring. Biodistribution studies for (18)F-RGD2 revealed favorable in vivo pharmacokinetic properties, with significant levels of receptor-specific tumor uptake determined via blocking studies. MicroPET imaging results demonstrated high contrast visualization of SKOV-3 tumors. And tumor to background ratio (T/NT) of (18)F-RGD2 uptake was significantly higher than that of (18)F-FDG. Studies on antiangiogenic therapy demonstrated percentage of injected dose per gram of tissue (%ID/g) tumor uptake of (18)F-RGD2 which was obviously decreased in the treatment group than the control group, especially at 60 min (by 31.31 ± 7.18 %, P = 0.009) and 120 min (by 38.92 ± 8.31 %, P < 0.001) after injection of (18)F-RGD2. MVD measurement of SKOV-3 tumors confirmed the finding of the biodistribution studies in monitoring antiangiogenesis therapy. (18)F-RGD2, with favorable biodistribution properties and specific affinity, is a promising tracer for tumor imaging and monitoring antiangiogenesis therapy in ovarian cancer SKOV-3 xenograft-bearing mice.
authors.affiliation: Department of Nuclear Medicine, Qilu Hospital, Shandong University, No.107 Wenhuaxi Road, Jinan, Shandong, China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Yang
authors.forename: Pei
authors.initials: P
authors.lastname: Nie
authors.forename: Yu
authors.initials: Y
authors.lastname: Kong
authors.forename: Hukui
authors.initials: H
authors.lastname: Sun
authors.forename: Guihua
authors.initials: G
authors.lastname: Hou
authors.forename: Jiankui
authors.initials: J
authors.lastname: Han
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C000600090:FB-NH-PEG4-E(PEG4-c(RGDfK))2; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D017239:Paclitaxel