title: Image-guided PO2 probe measurements correlated with parametric images derived from 18F-fluoromisonidazole small-animal PET data in rats.
abstract: (18)F-fluoromisonidazole PET, a noninvasive means of identifying hypoxia in tumors, has been widely applied but with mixed results, raising concerns about its accuracy. The objective of this study was to determine whether kinetic analysis of dynamic (18)F-fluoromisonidazole data provides better discrimination of tumor hypoxia than methods based on a simple tissue-to-plasma ratio.
  
  
  METHODS
  Eleven Dunning R3327-AT prostate tumor-bearing nude rats were immobilized in custom-fabricated whole-body molds, injected intravenously with (18)F-fluoromisonidazole, and imaged dynamically for 105 min. They were then transferred to a robotic system for image-guided measurement of intratumoral partial pressure of oxygen (Po(2)). The dynamic (18)F-fluoromisonidazole uptake data were fitted with 2 variants of a 2-compartment, 3-rate-constant model, one constrained to have K(1) equal to k(2) and the other unconstrained. Parametric images of the rate constants were generated. The Po(2) measurements were compared with spatially registered maps of kinetic rate constants and tumor-to-plasma ratios.
  
  
  RESULTS
  The constrained pharmacokinetic model variant was shown to provide fits similar to that of the unconstrained model and did not introduce significant bias in the results. The trapping rate constant, k(3), of the constrained model provided a better discrimination of low Po(2) than the tissue-to-plasma ratio or the k(3) of the unconstrained model.
  
  
  CONCLUSIONS
  The use of kinetic modeling on a voxelwise basis can identify tumor hypoxia with improved accuracy over simple tumor-to-plasma ratios. An effective means of controlling noise in the trapping rate constant, k(3), without introducing significant bias, is to constrain K(1) equal to k(2) during the fitting process.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Bartlett
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Beattie
authors.forename: Manoj
authors.initials: M
authors.lastname: Naryanan
authors.forename: Jens-Christoph
authors.initials: JC
authors.lastname: Georgi
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Sean D
authors.initials: SD
authors.lastname: Carlin
authors.forename: Gordon
authors.initials: G
authors.lastname: Roble
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Donoghue
authors.forename: Alexander
authors.initials: A
authors.lastname: Fischer
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D007700:Kinetics; D008297:Male; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011312:Pressure; D051381:Rats; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology
chemical_list: C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen