Assessing regional hypoxia in human renal tumours using ¹⁸F-fluoromisonidazole positron emission tomography

OBJECTIVE: To assess renal tumours for hypoxic regions using ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) positron emission tomography (PET), a recognized noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma (RCC) can be potentially cured with nephrectomy but recurrence develops in most patients, who then respond poorly to treatments such as chemotherapy, and hypoxia is known to confer resistance to radiotherapy and chemotherapy in many solid tumours. PATIENTS AND METHODS: In all, 17 patients had ¹⁸F-FMISO PET scans before nephrectomy for presumed RCC. Specimens were examined histologically, and immunohistochemistry was used to compare the microvessel density (MVD) as an indicator of angiogenesis in the tumour and normal parenchyma, in 15 patients. Tumour oxygenation was measured invasively in three patients using a polarographic oxygen sensor probe. RESULTS: Of the 15 patients with histological results, 11 had RCC and four had other tumours. Although there was a trend there was no statistically significant (P = 0.14) difference in the maximum standardized uptake value (SUV_max) when comparing the region of the kidney involved with RCC; the mean (95% confidence interval) SUV_max in the tumours was 1.3 (0.15), whilst that in the normal contralateral kidney was 1.1 (0.22). The MVD was greater in RCC, at 13.7 (3.1) mean vessels per high-power field than in normal tissue, at 6.9 (1.9). Hypoxia as measured polarographically was detected in three RCCs (median pO₂ 9.6 mmHg) compared to normal parenchyma at 37.6 mmHg. CONCLUSIONS: Although ¹⁸F-FMISO scans showed significant uptake in other solid tumours, there was only mild ¹⁸F-FMISO uptake in the present RCCs. The invasive measurements indicated that there was hypoxia in RCC, but the median pO₂ did not fall below 9.5 mmHg. Further direct studies of renal tumour oxygenation combined with therapies directed towards hypoxia may allow a better understanding of the relationship between ¹⁸F-FMISO results and the biological significance of hypoxia in RCC.