Tumoral Hypoxia in Osteosarcoma in Rats: Preliminary Study of Blood Oxygenation Level–Dependent Functional MRI and 18F-Misonidazole PET/CT With Diffusion-Weighted MRI Correlation

Abstract

The prognostic implication of oxygen concentration as a factor in recurrence of solid tumors has been proved. Hypoxic osteosarcoma, imaged with (18)F-misonidazole PET/CT, is the most frequent primary malignant bone tumor. The aim of our study was to determine the role of blood oxygenation level-dependent (BOLD) functional MRI in an osteosarcoma rodent model by comparison of oxygenation levels in BOLD functional MRI and (18)F-misonidazole PET/CT and correlating the findings with those of diffusion-weighted MRI (DWI). After validation of a hypoxic rodent model, 3-T MRI of osteosarcoma grafted in eight rats, including anatomic, DWI, and BOLD sequences in ambient air and after 2 and 3 minutes of impregnation of 8 L/min of oxygen, was performed on days 10, 17, and 24 after tumor grafting. (18)F-misonidazole PET/CT was performed on day 26, and the rats were sacrificed on day 27 for specific screening of markers of hypoxia. We measured BOLD signal intensity in tumors and normal tissue and compared these results with those on apparent diffusion coefficient maps and (18)F-misonidazole uptake according to maximum standardized uptake value ratio between tumor and healthy spongy bone. Hypoxia was confirmed by histologic study in all cases. We found a significant difference (day 17, p = 0.0038; day 24, p = 0.0051) in the decrease in signal intensity of hypoxic tumor in the presence of oxygen compared with ambient air without relation to duration of oxygen impregnation (p = 0.06). We found a significant correlation (p = 0.003) between BOLD signal intensity and maximum standardized uptake value at (18)F-misonidazole PET/CT. We found no correlation between the decrease in BOLD signal intensity and apparent diffusion coefficient (p = 0.07). BOLD functional MRI may be a promising tool for noninvasive functional imaging of bone tumors, but additional developments are necessary to permit its use in clinical practice.