Preclinical evaluation of parametric image reconstruction of [18F]FMISO PET: correlation with ex vivo immunohistochemistry

Compared to indirect methods, direct parametric image reconstruction (PIR) has the advantage of high quality and low statistical errors. However, it is not yet clear if this improvement in quality is beneficial for physiological quantification. This study aimed to evaluate direct PIR for the quantification of tumor hypoxia using the hypoxic fraction (HF) assessed from immunohistological data as a physiological reference. Sixteen mice with xenografted human squamous cell carcinomas were scanned with dynamic [18F]FMISO PET. Afterward, tumors were sliced and stained with H&E and the hypoxia marker pimonidazole. The hypoxic signal was segmented using k-means clustering and HF was specified as the ratio of the hypoxic area over the viable tumor area. The parametric Patlak slope images were obtained by indirect voxel-wise modeling on reconstructed images using filtered back projection and ordered-subset expectation maximization (OSEM) and by direct PIR (e.g., parametric-OSEM, POSEM). The mean and maximum Patlak slopes of the tumor area were investigated and compared with HF. POSEM resulted in generally higher correlations between slope and HF among the investigated methods. A strategy for the delineation of the hypoxic tumor volume based on thresholding parametric images at half maximum of the slope is recommended based on the results of this study.