title: 18F-Fluoromisonidazole Quantification of Hypoxia in Human Cancer Patients Using Image-Derived Blood Surrogate Tissue Reference Regions.
abstract: (18)F-fluoromisonidazole ((18)F-FMISO) is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. (18)F-FMISO equilibrates in normoxic tissues but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood (TB) ratio is suitable for quantifying hypoxia. A TB ratio threshold of 1.2 or greater is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling.
  
  
  METHODS
  Patients underwent 20-min (18)F-FMISO scanning during the 90- to 140-min interval after injection with venous blood sampling. Two hundred twenty-three (18)F-FMISO patient studies had detectable surrogate blood regions in the field of view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared with values using surrogate blood regions derived from the heart, aorta, or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from the cerebellum were compared for their ability to independently predict outcome.
  
  
  RESULTS
  Vascular regions of heart showed the highest correlation to measured blood activity (R(2) = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had predictive power nearly identical to parameters derived from blood, thus obviating the need for venous sampling in these patients.
  
  
  CONCLUSIONS
  Simple static analysis of (18)F-FMISO PET captures both the intensity (TBmax) and the spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia.
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington muzi@uw.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Muzi
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Lanell M
authors.initials: LM
authors.lastname: Peterson
authors.affiliation: School of Mathematics, Department of Statistics, University College Cork, Cork, Ireland.
authors.forename: Janet N
authors.initials: JN
authors.lastname: O'Sullivan
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: James R
authors.initials: JR
authors.lastname: Fink
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rajendran
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Lena J
authors.initials: LJ
authors.lastname: McLaughlin
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington muzi@uw.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Muzi
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Krohn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D002531:Cerebellum / Q000000981:diagnostic imaging; D018450:Disease Progression; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis / Q000000981:diagnostic imaging*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D009369:Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D010100:Oxygen / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen
keywords: 18F-FMISO; PET; hypoxia; quantitation