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Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with 18F-Fluoroazomycin Arabinoside and 15O-H2O PET

18F-fluoroazomycin arabinoside (18F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of 18F-FAZA may be compromised, potentially disturbing the association between tissue hypoxia and 18F-FAZA uptake. The aim of this study was to gain insight into the relationship between tumor perfusion and 18F-FAZA uptake. Methods: Ten patients diagnosed with advanced non–small cell lung cancer underwent subsequent dynamic 15O-H2O and 18F-FAZA PET scans with arterial sampling. Parametric images of both 15O-H2O–derived perfusion (tumor blood flow [TBF]) and volume of distribution (VT) of 18F-FAZA were generated. Next, multiparametric classification was performed using lesional and global thresholds. Voxels were classified as low or high TBF and 18F-FAZA VT, respectively. Finally, by combining these initial classifications, voxels were allocated to 4 categories: lowTBF–lowVT, lowTBF–highVT, highTBF–lowVT, and highTBF–highVT. Results: A total of 13 malignant lesions were identified in the 10 patients. The TBF and 18F-FAZA VT values (average ± SD) across all lesions were 0.45 ± 0.20 mL·cm−3·min−1 and 0.94 ± 0.31 mL·cm−3, respectively. The averages of all lesional median values for TBF and 18F-FAZA VT were 0.37 ± 0.15 mL·cm−3·min−1 and 0.85 ± 0.18 mL·cm−3, respectively. Multiparametric analysis showed that classified voxels were clustered rather than randomly distributed. Several intralesion areas were identified where 18F-FAZA VT was inversely related to TBF. On the other hand, there were also distinct areas where TBF as well as 18F-FAZA VT were decreased or increased. Conclusion: The present data indicate that spatial variation of 18F-FAZA uptake is not necessarily inversely related to TBF. This suggests that decreased TBF may result in flow-limited delivery of 18F-FAZA. Areas with both high 18F-FAZA uptake and high TBF values suggest that high 18F-FAZA uptake, possibly suggesting hypoxia, may occur despite high TBF values. In conclusion, multiparametric evaluation of the spatial distributions of both TBF and 18F-FAZA uptake may be helpful for understanding the 18F-FAZA signal.