Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms. Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (Aimage) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV+2cm). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between Aimage and Aadmin and between mean dose estimates (DLDM, DVSV, DLDM-KA) for PV, T, and perfused NL volumes. While Aadmin and Aimage in PV were highly correlated (R2>0.95), the mean bias±standard error (SE) and (95% limits of agreement, LOA) was significantly non-zero with -22.7±4.7% (±28.4%). In PV+2cm, the mean bias±SE (±LOA) decreased to 1.3±3.4% (±18.0%) consistent with zero mean error. DLDM and DVSV were highly correlated (R2>0.99) for all volumes of interest (VOIs) and the meanbias±SE(±LOA) was 2.2±0.2% (±1.0%), 0.7±0.4% (±2.8%), and 3.2±0.5% (±2.8%) for PV, T, and NL, respectively. DLDM-KA and DVSV were correlated with R2=0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The meanbias±SE(±LOA) between DLDM-KA and DVSV was significantly non-zero with -19.6±5.1% (±31.0%), -20.8±4.4% (±29.0%), and -18.1±5.3% (±31.1%) for PV, T, and NL, respectively. The summation of Aimage in PV was underestimated relative to Aadmin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was Aimage, on average, equal to Aadmin. The differences between DLDM and DVSV were not clinically relevant, though DLDM-KA was approximately 20% greater than DVSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate 90Y-PET/CT quantification, LDMKA is the preferred algorithm for accurate 90Y-PET/CT-based dosimetry following 90Y-RE.
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