Effect of intratumoral heterogeneity in oxygenation status on FMISO PET, autoradiography, and electrode Po2 measurements in murine tumors

Purpose: 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 [F-18]fluoromisonidazole (FMISO). Methods and Materials: We compared the 2 methods in conjunction with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) PET, dual-tracer ex vivo autoradiography (FMISO and 2-deoxy-D-[1-C-14]glucose (2DG)), and histology in 2 murine tumor models, the C3H mammary carcinoma and the SCCVII squamous cell carcinoma. Results: 2-[F-18]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. (c) 2005 Elsevier Inc.