Noninvasive multimodality imaging of the tumor microenvironment: Registered dynamic magnetic resonance imaging and positron emission tomography studies of a preclinical tumor model of tumor hypoxia(1,2) Journal Article


Authors: Cho, H.; Ackerstaff, E.; Carlin, S.; Lupu, M. E.; Wang, Y.; Rizwan, A.; O'Donoghue, J.; Ling, C. Clifton; Humm, J. L.; Zanzonico, P. B.; Koutcher, J. A.
Article Title: Noninvasive multimodality imaging of the tumor microenvironment: Registered dynamic magnetic resonance imaging and positron emission tomography studies of a preclinical tumor model of tumor hypoxia(1,2)
Abstract: In vivo knowledge of the spatial distribution of viable, necrotic, and hypoxic areas can provide prognostic information about the risk of developing metastases and regional radiation sensitivity and may be used potentially for localized dose escalation in radiation treatment. In this study, multimodality in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging using stereotactic fiduciary markers in the Dunning R3327-AT prostate tumor were performed, focusing on the relationship between dynamic contrast-enhanced (DCE) MRI using Magnevist (Gd-DTPA) and dynamic (18)F-fluoromisonidazole ((18)F-Fmiso) PET. The noninvasive measurements were verified using tumor tissue sections stained for hematoxylin/eosin and pimonidazole. To further validate the (18)relationship between (18)F-Fmiso and pimonidazole uptake, (18)F digital autoradiography was performed on a selected tumor and compared with the corresponding pimonidazole-stained slices. The comparison of Akep values (kep = rate constant of movement of Gd-DTPA between the interstitial space and plasma and A = amplitude in the two-compartment model (Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995). Magn Reson Med 33, 506-514) derived from DCE-MRI studies and from early (18)F-Fmiso uptake PET studies showed that tumor vasculature is a major determinant of early (18)F-Fmiso uptake. A negative correlation between the spatial map of Akep and the slope map of late (last 1 hour of the dynamic PET scan) (18)F-Fmiso uptake was observed. The relationships between DCE-MRI and hematoxylin/eosin slices and between (18)F-Fmiso PET and pimonidazole slices confirm the validity of MRI/PET measurements to image the tumor microenvironment and to identify regions of tumor necrosis, hypoxia, and well-perfused tissue.© 2009 Neoplasia Press, Inc. All rights reserved.
Keywords: nonhuman; nuclear magnetic resonance imaging; positron emission tomography; methodology; magnetic resonance imaging; radiopharmaceuticals; animal cell; animal; animals; animal experiment; animal model; pathology; hypoxia; prostatic neoplasms; disease model; diagnostic agent; drug uptake; diagnostic value; contrast enhancement; prostate tumor; rat; positron-emission tomography; radiopharmaceutical agent; drug derivative; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol f 18; pimonidazole; cell hypoxia; rats; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol; misonidazole; disease models, animal; image processing, computer-assisted; gadolinium pentetate; image processing; tumor vascularization; stereotactic procedure; nitroimidazole derivative; autoradiography; tumor diagnosis; nitroimidazoles
Journal Title: NeoPlasia
Volume: 11
Issue: 3
ISSN: 1522-8002
Publisher: Elsevier Science Inc.  
Date Published: 2009-03-01
Start Page: 247
End Page: 259
Language: English
DOI: 10.1593/neo.81360
PUBMED: 19242606
PROVIDER: scopus
PMCID: PMC2647727
DOI/URL:
Notes: Corrigendum issued, see DOI: 10.1016/j.neo.2016.10.008 -- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: NEOPF" - "Source: Scopus"
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MSK Authors
  1. Hyung Joon Cho
    8 Cho
  2. John Laurence Humm
    433 Humm
  3. Pat B Zanzonico
    355 Zanzonico
  4. Jason A Koutcher
    278 Koutcher
  5. Sean Denis Carlin
    83 Carlin
  6. C Clifton Ling
    331 Ling
  7. Asif Rizwan
    9 Rizwan
  8. Mihaela E Lupu
    10 Lupu
  9. Ya Wang
    20 Wang