TY - JOUR
T1 - Imaging hypoxia after oxygenation-modification
T2 - Comparing [ 18F]FMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors
AU - Troost, Esther G.C.
AU - Laverman, Peter
AU - Kaanders, Johannes H.A.M.
AU - Philippens, Mariëlle
AU - Lok, Jasper
AU - Oyen, Wim J.G.
AU - van der Kogel, Albert J.
AU - Boerman, Otto C.
AU - Bussink, Johan
N1 - Funding Information:
This research was supported by EC FP6 funding (Biocare – Contract no. LSHC-CT-2004-505785) and by Grant KUN 2003-2901 of the Dutch Cancer Society. We thank Dr. J.A. Raleigh for the gift of anti-pimonidazole MAb, Dr. H. Rennen for the synthesis of [ 18 F]FMISO and the collaborators from the Central Animal Laboratory for biotechnical assistance and animal care.
PY - 2006/8
Y1 - 2006/8
N2 - Purpose: Hypoxia is one of the reasons for radiation therapy resistance. Positron emission tomography using 18F-labeled misonidazole ([ 18F]FMISO) is a non-invasive method of imaging tumor hypoxia. Aim of this study was to validate [ 18F]FMISO against the clinically most widely used hypoxic cell marker pimonidazole under different oxygenation conditions. Materials and methods: One human head and neck squamous cell carcinoma (SCCNij3) and two human glioblastoma (E102 and E106) xenograft tumor lines were studied after injection of [ 18F]FMISO and pimonidazole. Control mice were compared with a second group breathing carbogen to reduce tumor hypoxia and with a third group with clamped tumors to increase hypoxia. Tumor sections were analyzed on a phosphor imaging system and consecutively stained immunohistochemically (IHC) for visualization of pimonidazole. Pixel-by-pixel analysis was performed and the hypoxic fraction, obtained after segmentation of the pimonidazole signal, was related to the mean optical density of [ 18F]FMISO and pimonidazole. Results: A moderate pixel-by-pixel correlation between [ 18F]FMISO autoradiography and pimonidazole IHC was found for the control tumors, after carbogen breathing and after clamping for SCCNij3. For E102 and E106, mean signal intensities for pimonidazole significantly decreased after carbogen breathing and increased after clamping, mean [ 18F]FMISO signal intensities increased significantly after clamping and a significant correlation between the hypoxic fractions and the mean [ 18F]FMISO signal intensities was found. Conclusions: [ 18F]FMISO autoradiography and pimonidazole immunohistochemistry can both be used to visualize treatment induced changes in tumor hypoxia. However, the response to these modifications differs widely between xenograft tumor lines.
AB - Purpose: Hypoxia is one of the reasons for radiation therapy resistance. Positron emission tomography using 18F-labeled misonidazole ([ 18F]FMISO) is a non-invasive method of imaging tumor hypoxia. Aim of this study was to validate [ 18F]FMISO against the clinically most widely used hypoxic cell marker pimonidazole under different oxygenation conditions. Materials and methods: One human head and neck squamous cell carcinoma (SCCNij3) and two human glioblastoma (E102 and E106) xenograft tumor lines were studied after injection of [ 18F]FMISO and pimonidazole. Control mice were compared with a second group breathing carbogen to reduce tumor hypoxia and with a third group with clamped tumors to increase hypoxia. Tumor sections were analyzed on a phosphor imaging system and consecutively stained immunohistochemically (IHC) for visualization of pimonidazole. Pixel-by-pixel analysis was performed and the hypoxic fraction, obtained after segmentation of the pimonidazole signal, was related to the mean optical density of [ 18F]FMISO and pimonidazole. Results: A moderate pixel-by-pixel correlation between [ 18F]FMISO autoradiography and pimonidazole IHC was found for the control tumors, after carbogen breathing and after clamping for SCCNij3. For E102 and E106, mean signal intensities for pimonidazole significantly decreased after carbogen breathing and increased after clamping, mean [ 18F]FMISO signal intensities increased significantly after clamping and a significant correlation between the hypoxic fractions and the mean [ 18F]FMISO signal intensities was found. Conclusions: [ 18F]FMISO autoradiography and pimonidazole immunohistochemistry can both be used to visualize treatment induced changes in tumor hypoxia. However, the response to these modifications differs widely between xenograft tumor lines.
KW - [ F]Fluoromisonidazole
KW - Carbogen
KW - Digital autoradiography
KW - Hypoxia
KW - Pimonidazole
UR - http://www.scopus.com/inward/record.url?scp=33748185692&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2006.07.023
DO - 10.1016/j.radonc.2006.07.023
M3 - Article
C2 - 16905213
AN - SCOPUS:33748185692
SN - 0167-8140
VL - 80
SP - 157
EP - 164
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 2
ER -