Hypoxia imaging with the nitroimidazole 18F-FAZA PET tracer: A comparision with OxyLite, EPR oxymetry and 19F-MRI relaxometry

Abstract

Background and purpose: Tumor hypoxia has been considered as an important prognosis factor in oncology. Quantitative information and distribution of oxygen concentration would be valuable for the improvement of therapeutic strategies. Given the importance of this aspect, there has been many techniques reported to be useful for hypoxia detection in tumors; but a limited number of methods have been implemented into clinical practice. One of techniques currently available for detection of hypoxia in human application is Positron Emission Tomography (PET). The accumulation of hypoxia-specific PET tracers can reflect hypoxic areas inside tumors that are relevant in terms of radiation resistance; however, this is an indirect method that cannot provide absolute values of pO2. Therefore, to evaluate the potential of PET hypoxia images with tracer 18F-fluoroazomycin-arabinoside (18F-FAZA), we compared PET hypoxia imaging to other oximetry techniques: Oxylite, Electron Paramagnetic Resonance (EPR) spectroscopy and Nuclear Magnetic Resonance Imaging by fluorine relaxometry (19F-MRI), respectively. Methods: Male adult WAG/Rij rats grafted with rhabdomyosarcoma in thighs were used for this study. In all comparisons, animals were randomly divided into two groups, breathing either room air or carbogen. PET imaging was performed on a dedicated small-animal PET scanner 3h after intravenous injection of 18.5-29.6 MBq 18F-FAZA. The median pO2 value of each tumor measured by Oxylite was calculated from the measurement at ten independent sites within the tumor. EPR acquisition was carried out 24h after charcoal implantation by using an L-band EPR spectrometer. For MRI oximetry, perfluoro-15-crown-5ether (15C5) was used as oxygen sensitive sensor, the spin-lattice relaxation time (T1) of 19F nuclei was acquired by an 11.7 T system with a tunable 1H/19F surface coil. Linewidth of EPR spectra and T1-value obtained by MRI were then converted to pO2 using the calibration curves. Results: The results from both Oxylite and EPR showed an increase of pO2 in the breathing carbogen group. In accordance with this tendency, the tumor-to-background (T/B) ratio measured by PET under high oxygen condition exhibited about 1.3-fold decrease than that under normoxic condition. The scatter-plots of T/B ratio versus measured pO2 were traced by using data from all individual tumors. There was a good correlation between the results obtained by PET and EPR (R = 0.93). In the case of Oxylite, although the poorer correlation coefficient was observed (R = 0.55), the trend for two values to agree was still related to the inverse function theoretically predicted. For the comparison of 18F-FAZA and 15C5 marker, we could not found the significant difference in values T1. This could be explained by the lower sensitivity of 19F-relaxometry compared to EPR and OxyLite. Conclusions: Our present study demonstrated a clear correlation between 18F-FAZA-PET signal intensities and tumor oxygenation. These results suggest that 18F-FAZA is an effective surrogate of hypoxia fractions and support the use of 18F-FAZA PET as an imaging technique to guide cancer therapy