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 (V_T) of [¹⁸F]FAZA. Next, multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high V_T using median tumour values across each scan. By combining these initial classifications, voxels were allocated to 4 categories (low perfusion-low V_T, low perfusion-high V_T, high perfusion-low V_T and high perfusion-high V_T).

Results 11 malignant lesions were identified in 8 patients. Average perfusion and V_T 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 V_T, respectively. Multiparametric analysis suggested that classified voxels were clustered rather than randomly distributed. Several intralesional areas could be identified where V_T of [¹⁸F]FAZA was inversely related to perfusion. Also distinct areas could be seen where perfusion and V_T 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.