@article {Iqbal530, author = {Ramsha Iqbal and Gem M. Kramer and Eline E. Verwer and Marc C. Huisman and Adrianus J. de Langen and Idris Bahce and Floris H.P. van Velden and Albert D. Windhorst and Adriaan A. Lammertsma and Otto S. Hoekstra and Ronald Boellaard}, title = {Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with 18F-Fluoroazomycin Arabinoside and 15O-H2O PET}, volume = {57}, number = {4}, pages = {530--535}, year = {2016}, doi = {10.2967/jnumed.115.166579}, publisher = {Society of Nuclear Medicine}, abstract = {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{\textendash}small cell lung cancer underwent subsequent dynamic 15O-H2O and 18F-FAZA PET scans with arterial sampling. Parametric images of both 15O-H2O{\textendash}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{\textendash}lowVT, lowTBF{\textendash}highVT, highTBF{\textendash}lowVT, and highTBF{\textendash}highVT. Results: A total of 13 malignant lesions were identified in the 10 patients. The TBF and 18F-FAZA VT values (average {\textpm} SD) across all lesions were 0.45 {\textpm} 0.20 mL{\textperiodcentered}cm-3{\textperiodcentered}min-1 and 0.94 {\textpm} 0.31 mL{\textperiodcentered}cm-3, respectively. The averages of all lesional median values for TBF and 18F-FAZA VT were 0.37 {\textpm} 0.15 mL{\textperiodcentered}cm-3{\textperiodcentered}min-1 and 0.85 {\textpm} 0.18 mL{\textperiodcentered}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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/57/4/530}, eprint = {https://jnm.snmjournals.org/content/57/4/530.full.pdf}, journal = {Journal of Nuclear Medicine} }