Image-guided PO(2) probe measurements correlated with parametric images derived from (18)F-fluoromisonidazole small-animal PET data in rats Journal Article


Authors: Bartlett, R. M.; Beattie, B. J.; Naryanan, M.; Georgi, J. C.; Chen, Q.; Carlin, S. D.; Roble, G.; Zanzonico, P. B.; Gonen, M.; O'Donoghue, J.; Fischer, A.; Humm, J. L.
Article Title: Image-guided PO(2) probe measurements correlated with parametric images derived from (18)F-fluoromisonidazole small-animal PET data in rats
Abstract: 18F-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 18F-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 18F-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 18F-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. Copyright © 2012 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Keywords: controlled study; nonhuman; positron emission tomography; diagnostic accuracy; animal tissue; image analysis; oxygen; animal experiment; animal model; hypoxia; drug uptake; rat; intermethod comparison; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol f 18; oxygen tension; molecular probe; autoradiography; fluorescence imaging; kinetic modeling; diagnostic test accuracy study; oxygen tissue level; [; 18f]-fluoromisonidazole; 18f]-fmiso; oxylite probe; parametric images
Journal Title: Journal of Nuclear Medicine
Volume: 53
Issue: 10
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2012-10-01
Start Page: 1608
End Page: 1615
Language: English
DOI: 10.2967/jnumed.112.103523
PROVIDER: scopus
PUBMED: 22933821
PMCID: PMC3784982
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Mithat Gonen
    1031 Gonen
  2. John Laurence Humm
    436 Humm
  3. Pat B Zanzonico
    357 Zanzonico
  4. Gordon Roble
    9 Roble
  5. Sean Denis Carlin
    83 Carlin
  6. Bradley Beattie
    131 Beattie
  7. Qing Chen
    19 Chen