Effect of intratumoral heterogeneity in oxygenation status on FMISO PET, autoradiography, and electrode Po2 measurements in murine tumors.
OBJECTIVE
To explore conflicting results obtained when tumor hypoxia is assessed with Eppendorf electrode Po(2) measurements and with positron emission tomography (PET) by use of [(18)F]fluoromisonidazole (FMISO).


METHODS
We compared the 2 methods in conjunction with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) PET, dual-tracer ex vivo autoradiography (FMISO and 2-deoxy-D-[1-(14)C]glucose (2DG)), and histology in 2 murine tumor models, the C3H mammary carcinoma and the SCCVII squamous cell carcinoma.


RESULTS
2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-PET showed tumor-to-reference tissue ratios of 3.5 in both tumor models after 2 hours. C3H mammary carcinoma reached an FMISO PET ratio of 11 after 3.5 hours. Autoradiography showed large confluent areas of FMISO and 2DG uptake. Median Po(2) was 7 mm Hg and necrotic fraction was 10% to 30%. SCCVII squamous-cell carcinoma reached an FMISO PET tumor-to-reference tissue ratio of 2 after 2.5 hours. Autoradiography showed homogeneous 2DG uptake and scattered foci of high FMISO uptake. Median Po(2) was 1 mm Hg and necrotic fraction was below 5%.


CONCLUSIONS
Ex vivo dual-tracer autoradiography documented the ability of in vivo FMISO PET to distinguish between confluent areas of either viable tissue or necrosis. Electrode Po(2) measurements could not be ascribed to specific areas in the tumors. Less uptake of FMISO in SCCVII squamous-cell carcinoma than in C3H mammary carcinoma could be caused by scattered foci versus confluent areas of viable hypoxic tissue in the 2 tumors, respectively.
Sørensen
Michael
M
PET Center, Aarhus University Hospital, Aarhus, Denmark. michael@pet.auh.dk
Horsman
Michael R
MR
Cumming
Paul
P
Munk
Ole Lajord
OL
Keiding
Susanne
S
D000818:Animals; D001345:Autoradiography / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010101:Oxygen Consumption; D010313:Partial Pressure; D049268:Positron-Emission Tomography; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole