title: Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography.
abstract: OBJECTIVE
  Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation.
  
  
  METHODS
  Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio > or = 1.4 by 120 min after injection. Serial FHVs were compared for each patient.
  
  
  RESULTS
  Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV.
  
  
  CONCLUSIONS
  Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.
authors.affiliation: Department of Radiation Oncology, University of Washington School of Medicine, Seattle, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Koh
authors.forename: K S
authors.initials: KS
authors.lastname: Bergman
authors.forename: J S
authors.initials: JS
authors.lastname: Rasey
authors.forename: L M
authors.initials: LM
authors.lastname: Peterson
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: M M
authors.initials: MM
authors.lastname: Graham
authors.forename: J R
authors.initials: JR
authors.lastname: Grierson
authors.forename: K L
authors.initials: KL
authors.lastname: Lindsley
authors.forename: T K
authors.initials: TK
authors.lastname: Lewellen
authors.forename: K A
authors.initials: KA
authors.lastname: Krohn
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D010101:Oxygen Consumption; D011838:Radiation-Sensitizing Agents; D014055:Tomography, Emission-Computed
chemical_list: D011838:Radiation-Sensitizing Agents; C031843:fluoromisonidazole; D008920:Misonidazole