title: Predictive Value of Early-Stage Uptake of 3'-Deoxy-3'-18F-Fluorothymidine in Cancer Cells Treated with Charged Particle Irradiation.
abstract: The aim of this study was to investigate whether 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) can monitor the early response of tumor cell proliferation to charged particle irradiation in vitro and in vivo.
  
  
  METHODS
  In vitro, after 0.1, 0.5, 1, 5, and 10 Gy of proton or carbon ion irradiation, (18)F-FLT cell uptake was examined at 24 h and cell proliferation ability was measured from days 1 to 4. In vivo, after 0.5, 1, and 5 Gy of proton or carbon ion irradiation, (18)F-FLT PET imaging was performed on tumor-bearing BALB/c nu/nu mice at 24 h and tumor growth was measured from days 1 to 7. Tumor-to-background ratios of standardized uptake values were calculated to assess the (18)F-FLT accumulation in tumors. Both cells and mice also received x-irradiation as a control.
  
  
  RESULTS
  In vitro, (18)F-FLT cell uptake was significantly lower after 1 Gy of proton irradiation (P < 0.05) and carbon ion irradiation (P < 0.05) and after 5 Gy of x-irradiation (P < 0.01), but cell proliferation ability at these doses did not show significant differences until day 3. In vivo, (18)F-FLT tumor uptake was significantly lower after 1 Gy of proton (P < 0.001) and carbon ion irradiation (P < 0.01) and after 5 Gy of x-irradiation (P < 0.001), but tumor growth did not significantly differ at these doses until day 4 after proton irradiation, day 3 after carbon ion irradiation, and day 5 after x-irradiation.
  
  
  CONCLUSIONS
  The reduction in (18)F-FLT uptake after charged particle irradiation was more rapid than the change in tumor growth in vivo or the change in cell proliferation ability in vitro. Therefore, (18)F-FLT is a promising tracer for monitoring the early response of cancer to charged particle irradiation.
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Research and Development Division, Wakasa Wan Energy Research Center, Fukui, Japan; and.
authors.forename: Kyo
authors.initials: K
authors.lastname: Kume
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Martinez
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Fukui, Japan Research and Education Program for Life Science, University of Fukui, Fukui, Japan ykiyono@u-fukui.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D002244:Carbon / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D004307:Dose-Response Relationship, Radiation; D007477:Ions / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D010316:Particle Size; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D014965:X-Rays
chemical_list: D015224:Dideoxynucleosides; D007477:Ions; D019275:Radiopharmaceuticals; D002244:Carbon; C002854:alovudine
keywords: 3′-deoxy-3′-18F-fluorothymidine (18F-FLT); cell proliferation ability; charged particle irradiation; positron emission tomography (PET); tumor volume