A comparison of methods for in vivo activity and absorbed dose quantification with PET/CT following yttrium-90 radioembolization

Background: 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.

Purpose: 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.

Methods: Thirty-five patients underwent ⁹⁰Y-PET/CT imaging after ⁹⁰Y-RE with TheraSphere. The net administered ⁹⁰Y activity (A_admin) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (A_image) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV_{+2 cm}). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDM_KA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between A_image and A_admin and between mean dose estimates (D_LDM, D_VSV, D_LDM-KA) for PV, T, and perfused NL volumes.

Results: While A_admin and A_image 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_{+2 cm}, the mean bias ± SE (± LOA) decreased to 1.3 ± 3.4% (± 18.0%) consistent with zero mean error. D_LDM and D_VSV were highly correlated (R² > 0.99) for all volumes of interest (VOIs) and the mean bias ± 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. D_LDM-KA and D_VSV were correlated with R² = 0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The mean bias ± SE (± LOA) between D_LDM-KA and D_VSV 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.

Conclusions: The summation of A_image in PV was underestimated relative to A_admin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was A_image, on average, equal to A_admin. The differences between D_LDM and D_VSV were not clinically relevant, though D_LDM-KA was approximately 20% greater than D_VSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate ⁹⁰Y-PET/CT quantification, LDM_KA is the preferred algorithm for accurate ⁹⁰Y-PET/CT-based dosimetry following ⁹⁰Y-RE.