Image-Guided PO2 Probe Measurements Correlated with Parametric Images Derived from 18F-Fluoromisonidazole Small-Animal PET Data in Rats

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York.
Journal of Nuclear Medicine (Impact Factor: 6.16). 08/2012; 53(10):1608-15. DOI: 10.2967/jnumed.112.103523
Source: PubMed


(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.
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.
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.
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.

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Available from: Gordon S Roble, Apr 17, 2014
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    • "In accordance with this, we found significantly reduced k 3 -values for the HI-tumors, when we repeated the fitting of the TAC and additionally constrained k 4 to zero (data not shown). This would not be expected, if FMISO is irreversibly bound to hypoxic cells [26], and suggests that the two-tissue compartment model, might have some limitations when applied to the HI-subline. In agreement to our findings, Busk et al., concluded that a twocompartment model might be inappropriate in some tumor models [46]. "
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    • "Tracer Image Targeting Methods Application Species Authors 18 F-FMISO Hypoxia Voxelwise kinetic modeling Oncology/Prostate tumor Rat Bartlett et al. [23] "
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    • "The nitromidazole compound is usually assumed to be irreversibly bound to hypoxic regions. The irreversible two-tissue compartment has been reported to have the best physiological correlation with immunohistochemistry staining (Shi et al 2012) and oxygen tension (pO 2 ) measurements (Bartlett et al 2012). Therefore, the linearized irreversible two-compartment model, the Patlak plot, has been applied to produce hypoxia-related physiological parameters (Hong et al 2011). "
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