Comparison of (immuno-)fluorescence data with serial [¹⁸F]Fmiso PET/CT imaging for assessment of chronic and acute hypoxia in head and neck cancers.

PURPOSE

Both, acute and chronic hypoxia can have unfavorable impacts on tumor progression and therapy response. The aim of this study was to optimize a macroscopic technique for the quantification of acute and chronic hypoxia (Wang model assessment of serial [(18)F]Fmiso PET/CT imaging) by comparing with a microscopic technique [(immuno-)fluorescence staining in tumor cryosections].

MATERIALS AND METHODS

Tumor pieces from the human squamous cell carcinoma lines from the head and neck FaDu and CAL33 were xenografted into the hind leg of NMRI nu/nu mice. Tumor-bearing mice were placed on an in-house developed multi-point fixation system and subjected to two consecutive dynamic [(18)F]Fmiso PET/CTs within a 24h interval. The Wang model was applied to SUV (standard uptake values) to quantify the fractions of acute and chronic hypoxia. Hypoxia subtypes were also assessed in vital tumor tissue of cryosections from the same tumors for (immuno-)fluorescence distributions of Hoechst 33342 (perfusion), pimonidazole (hypoxia), and CD31 (endothelium) using pattern recognition in microcirculatory supply units (defined as vital tumor tissue area supplied by a single microvessel).

RESULTS

Using our multi-point fixation system, acceptable co-registration (registration errors ε ranged from 0.34 to 1.37) between serial PET/CT images within individual voxels was achieved. The Wang model consistently yielded higher fractions of acute hypoxia than the MCSU method. Through specific modification of the Wang model (Wang(mod)), it was possible to reduce the fraction of acute hypoxia. However, there was no significant correlation between the fractions of acute hypoxia in individual tumors assessed by the Wang(mod) model and the MCSU method for either tumor line (FaDu: r=0.68, p=0.21 and CAL33: r=0.71, p=0.18). This lack of correlation is most-likely due to the difference between the non-linear uptake of [(18)F]Fmiso and the spatial assessment of MCSUs.

CONCLUSIONS

Whether the Wang model can be used to predict radiation response after serial [(18)F]Fmiso PET imaging, needs to be confirmed in experimental and clinical studies.