Quantifying regional hypoxia in human tumors with positron emission tomography of [¹⁸F]fluoromisonidazole: A pretherapy study of 37 patients

Purpose: To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Methods and Materials: Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [¹⁸F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the intaged tumor volume with a tissue:blood [¹⁸F] activity ratio ≤ 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. Results: Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). Conclusions: Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O₂ electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.