(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.
Conclusion: 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.