Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies.
PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed primary brain tumors for the presence of hypoxia, as indicated by the uptake of 18F-fluoromisonidazole (18F-FMISO) and to examine the relationship of hypoxia to the uptake of 18F-FDG and molecular markers of hypoxia.


METHODS
Seventeen patients with suspected primary glioma were enrolled prospectively in this study. Sixteen patients had histology, with 2 having metastatic disease. All patients had PET studies with 18F-FMISO and 18F-FDG and MRI studies. Immunohistochemistry was undertaken with tumor markers of angiogenesis and hypoxia. Patients were monitored for disease progression and statistical analysis of data was performed.


RESULTS
Of the 14 patients with histology, 8 died with a median time of 16 mo (range, 2-30 mo) until death. Of those who died, 7 had positive and 1 had negative 18F-FMISO uptake. 18F-FMISO uptake was observed in all high-grade gliomas but not in low-grade gliomas. A significant relationship was found between 18F-FDG or 18F-FMISO uptake and expression of VEGF-R1 and Ki67 expression. Other immunohistochemical markers demonstrated a trend toward increased uptake but none was significant.


CONCLUSIONS
18F-FMISO PET provides a noninvasive assessment of hypoxia in glioma and was prognostic for treatment outcomes in the majority of patients. 18F-FMISO PET may have a role not only in directing patients toward targeted hypoxic therapies but also in monitoring response to such therapies.
Cher
Lawrence M
LM
Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia.
Murone
Carmel
C
Lawrentschuk
Nathan
N
Ramdave
Shanker
S
Papenfuss
Anthony
A
Hannah
Anthony
A
O'Keefe
Graeme J
GJ
Sachinidis
John I
JI
Berlangieri
Salvatore U
SU
Fabinyi
Gavin
G
Scott
Andrew M
AM
D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D001932:Brain Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D015687:Cell Hypoxia; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009389:Neovascularization, Pathologic / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013223:Statistics as Topic
D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole; D005947:Glucose; D010100:Oxygen