PET imaging of hypoxia
Hypoxia imaging with the nitroimidazole 18F-FAZA PET tracer: A comparison with OxyLite, EPR oximetry and 19F-MRI relaxometry

https://doi.org/10.1016/j.radonc.2012.04.011Get rights and content

Abstract

Background and purpose

18F-FAZA is a nitroimidazole PET tracer that can provide images of tumor hypoxia. However, it cannot provide absolute pO2 values. To qualify 18F-FAZA PET, we compared PET images to pO2 measured by OxyLite, EPR oximetry and 19F-MRI.

Materials and methods

Male WAG/Rij rats grafted with rhabdomyosarcoma were used. Tumor oxygenation was modified by gas breathing (air or carbogen). The same day of PET acquisition, the pO2 was measured in the same tumor either by OxyLite probes (measurement at 10 different sites), EPR oximetry using low frequency EPR or 19F-relaxometry using 15C5 on an 11.7 T MR system.

Results

There was a good correlation between the results obtained by PET and EPR (R = 0.93). In the case of OxyLite, although a weaker correlation 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 PET and 19F-MRI, no change in T1 was observed.

Conclusions

A clear correlation between 18F-FAZA PET image intensities and tumor oxygenation was demonstrated, suggesting that 18F-FAZA PET is a promising imaging technique to guide cancer therapy.

Section snippets

Animal and tumor model

Male adult WAG/Rij rats (Harlan Nederland, Horst, The Netherlands) weighting between 200 and 250 g were used for this study. Fragments of about 1 mm3 from a syngenic rhabdomyosarcoma were grafted subcutaneously in both thighs of each rat under general anesthesia by using intraperitoneal injection of a mixed solution of ketamine and xylazine (80 and 10 mg/kg, respectively). The experiments were performed when tumors grew to be 20–25 mm in diameter (at this size of tumor, the proportion of necrotic

Comparison between 18F-FAZA PET imaging and OxyLite oximetry

In this comparison (Fig. 2), animals were transferred to OxyLite system immediately after the PET scans. The mean ± SEM pO2 measured by OxyLite for the tumors used in normoxic condition was 1.89 ± 0.60 mm Hg, n = 11. A significant increase of this value was observed in the tumors of carbogen group (pO2 = 7.12 ± 1.74 mm Hg, n = 13). Similarly for PET imaging, 18F-FAZA exhibited a significant lower uptake in the case of carbogen (T/B ratio = 2.18 ± 0.71) than that of room air (T/B ratio = 2.90 ± 0.75). The best trend

Discussion

Considering the important role of tumor oxygenation, many hypoxia-targeting therapies have emerged and are being developed [35]. These therapeutic strategies, however, cannot be fully utilized unless we have a suitable method to assess hypoxia in routine clinical procedure. The current standard method [36] (Eppendorf measurements) is invasive and cannot provide three-dimensional heterogeneity of oxygenation. Moreover, these systems are not produced anymore by Eppendorf, and, consequently this

Acknowledgements

This work is supported by grants from Belgian National Fund for Scientific Research (FNRS), Televie, Fonds Joseph Maisin, Saint-Luc Foundation, Fondation contre le Cancer, “Actions de Recherches Concertées-Communauté Française de Belgique-ARC 09/14-020”.

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