title: 18F-fluromisonidazole PET imaging as a biomarker for the response to 5,6-dimethylxanthenone-4-acetic acid in colorectal xenograft tumors.
abstract: The aim of this study was to evaluate (18)F-fluromisonidazole ((18)F-FMISO) PET for monitoring the tumor response to the antivascular compound 5,6-dimethylxanthenone-4-acetic acid (DMXAA; vadimezan).
  
  
  METHODS
  (18)F-FMISO PET was performed 3 h before and 24 h after treatment with DMXAA (20 mg/kg) in mice bearing HT29 xenograft tumors. Pimonidazole was coadministered with the first (18)F-FMISO injection, and 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5) was coadministered with the second one. Hoechst 33342 was administered 5 min before sacrifice. Digital autoradiograms of tumor sections were acquired; this acquisition was followed by immunofluorescence microscopic visualization of pimonidazole, EF5, the Hoechst 33342, CD31, and α-smooth muscle actin.
  
  
  RESULTS
  DMXAA treatment resulted in a marked reduction in the (18)F-FMISO mean standardized uptake value (SUV(mean)) in approximately half of the treated tumors. The reduction in SUV(mean) correlated with a decrease in the fraction of tumor area staining positive for both EF5 and pimonidazole. Compared with untreated controls, tumors with decreasing SUV(mean) had significantly fewer perfused microvessels.
  
  
  CONCLUSIONS
  (18)F-FMISO PET could distinguish between different tumor responses to DMXAA treatment. However, a reduction in (18)F-FMISO SUV(mean) after DMXAA treatment was indicative of reduced perfusion and therefore delivery of (18)F-FMISO, rather than a reduction in tumor hypoxia.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Oehler
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lorenzen
authors.forename: C Clifton
authors.initials: CC
authors.lastname: Ling
authors.forename: Sean
authors.initials: S
authors.lastname: Carlin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008920:Misonidazole / Q000031:analogs & derivatives*; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D044004:Xanthones / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D044004:Xanthones; C031843:fluoromisonidazole; C066668:vadimezan; D008920:Misonidazole