Multiparametric evaluation of tumour hypoxia and perfusion using[15O]H2O and [18F]FAZA PET in NSCLC patients

Objectives [18F]fluoroazomycin-arabinoside ([18F]FAZA) is a PET tracer, proposed for quantifying tumour hypoxia. However, as hypoxia is associated with decreased perfusion, delivery of [18F]FAZA might be compromised, potentially disturbing the association between tissue hypoxia and [18F]FAZA uptake. This study aimed to gain insight in the relationship between tumour perfusion and [18F]FAZA uptake. Methods Eight patients with non-small cell lung cancer (NSCLC) underwent dynamic [15O]H2O and [18F]FAZA scans with arterial sampling. Parametric analyses were performed to generate quantitative 3D images of both perfusion and volume of distribution (VT) of [18F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high VT using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results 11 malignant lesions were identified in 8 patients. Average perfusion and VT across all lesions were 0.46±0.20 mL/mL/min and 0.95±0.31, respectively. The average of all median values across all lesions were 0.38±0.15 mL/mL/min and 0.87±0.18 for perfusion and VT, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where VT of [18F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and VT were either both decreased or increased. Conclusions Spatial variation of [18F]FAZA uptake is not necessarily inversely related with perfusion. Decreased perfusion might thus result in perfusion limited delivery of [18F]FAZA. In conclusion, multiparametric evaluation of the spatial distribution of both perfusion and [18F]FAZA uptake may be essential for understanding the [18F]FAZA signal.