title: Diversity of RGD radiotracers in monitoring antiangiogenesis of flavopiridol and paclitaxel in ovarian cancer xenograft-bearing mice.
abstract: BACKGROUND
  Although encouraging results had been shown in antiangiogenesis therapy monitoring, the underlying mechanism of RGD radiotracer accumulation needs to be further illustrated. This study was aimed to investigate the diversity of RGD radiotracers in monitoring antiangiogenic agent's effects and the underlying mechanism in ovarian cancer-bearing mice with a new agent flavopiridol compared with paclitaxel.
  
  
  METHODS
  Ovarian cancer SKOV-3 xenograft-bearing mice were established and divided into three groups, flavopiridol, paclitaxel and control. Flavopiridol (5mg/kg body weight) and paclitaxel (20mg/kg body weight) were administered every 3 days for 16 days. Tumor growth and proliferation were monitored by caliper measurements and immunofluorescence staining. Antiangiogenic effects were determined by tumor microvessel density (MVD) in vivo and by endothelial cell tube formation assay in vitro, respectively. (99m)Tc-3P-RGD2 was prepared, and its biodistribution studies were carried out. The effect of antiangiogenesis therapy on integrin αvβ3 expression was studied by immunohistochemical staining and flow cytometry.
  
  
  RESULTS
  Both paclitaxel and flavopiridol therapy could apparently inhibit tumor growth and proliferation, and antiangiogenic effects of therapy were validated in vivo and in vitro. However, compared with the control group, ID%/g tumor uptake of (99m)Tc-3P-RGD2 showed a significant decrease at 2 hours (by 39.96%±8.23%, P=0.044) and at 4 hours (by 35.76%±11.42%, P=0.024) post injection in the paclitaxel-treated group, but a slight increase of tumor uptake in the flavopiridol-treated group at 2 hours (by 4.42%±0.24%, p=0.898) and at 4 hours (by 12.2%±1.84%, P=0.702). The further studies indicated flavopiridol therapy has a dual-effect, reducing integrin αvβ3 expression on endothelial cells due to the reduction of tumor MVD and up-regulating the integrin αvβ3 expression on tumor cells.
  
  
  CONCLUSIONS
  There is diversity in evaluating antiangiogenic response when using (99m)Tc-3P-RGD2, which may be an important reminder in future clinical applications of RGD radiotracers as a strategy for antiangiogenesis therapy response monitoring.
authors.affiliation: Department of Nuclear Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Yang
authors.affiliation: Biomedical Isotope Research Center, School of Medicine, Shandong University, Jinan, China.
authors.forename: Hukui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Biomedical Isotope Research Center, School of Medicine, Shandong University, Jinan, China. Electronic address: ghhou1@hotmail.com.
authors.forename: Guihua
authors.initials: G
authors.lastname: Hou
authors.affiliation: Department of Nuclear Medicine, Qilu Hospital, Shandong University, Jinan, China. Electronic address: hanjiank@163.com.
authors.forename: Jiankui
authors.initials: J
authors.lastname: Han
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016903:Drug Monitoring; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D020533:Angiogenesis Inhibitors; D005419:Flavonoids; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010880:Piperidines; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; C077990:alvocidib; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel
keywords: (99m)Tc; Integrin αvβ3; Mechanism; Monitoring antiangiogenesis therapy; Ovarian cancer; RGD peptide