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Background The aim of this study was to compare predictive and post-treatment dosimetry and analyze the differences, investigating factors related to activity preparation and delivery, imaging modality used, and interventional radiology. Methods Twenty-three HCC patients treated by selective internal radiation therapy with 90 Y glass microspheres were included in this study. Predictive and post-treatment dosimetry were calculated at the voxel level based on 99m Tc-MAA SPECT/CT and 90 Y-microsphere PET/CT respectively. Dose distribution was analyzed through mean dose, metrics extracted from dose-volume histograms, and Dice similarity coefficients applied on isodoses. Reproducibility of the radiological gesture and its influence on dose deviation was evaluated. Results 90 Y delivered activity was lower than expected in 67% (16/24) of the cases mainly due to the residual activity. A mean deviation of − 6 ± 11% was observed between the delivered activity and the 90 Y PET’s FOV activity. In addition, a substantial difference of − 20 ± 8% was measured on 90 Y PET images between the activity in the liver and in the whole FOV. After normalization, 99m Tc-MAA SPECT dosimetry was highly correlated and concordant with 90 Y-microsphere PET dosimetry for all dose metrics evaluated ( ρ = 0.87, ρ c = 0.86, P = 3.10 −8 and ρ = 0.91, ρ c = 0.90, P = 7.10 −10 for tumor and normal liver mean dose respectively for example). Besides, mean tumor dose deviation was lower when the catheter position was identical than when it differed (16 Gy vs. 37 Gy, P = 0.007). Concordance between predictive and post-treatment dosimetry, evaluated with Dice similarity coefficients applied on isodoses, significantly correlated with the distance of the catheter position from artery bifurcation ( P = 0.04, 0.0004, and 0.05, for 50 Gy, 100 Gy, and 150 Gy isodoses respectively). Conclusions Discrepancies between planned activity and activity measured on 90 Y PET images were observed and seemed to be mainly related to clinical hazards and equipment issues. Predictive vs. post-treatment comparison of relative dose distributions between tumor and normal liver showed a good correlation and no significant difference highlighting the predictive value of 99m Tc MAA SPECT/CT-based dosimetry. Besides, the reproducibility of catheter tip position appears critical in the agreement between predictive and actual dose d...

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