Comparison of different methods for post-therapeutic dosimetry in [177Lu]Lu-PSMA-617 radioligand therapy

Background Dosimetry is of high importance for optimization of patient-individual PSMA-targeted radioligand therapy (PSMA-RLT). The aim of our study was to evaluate and compare the feasibility of different approaches of image-based absorbed dose estimation in terms of accuracy and effort in clinical routine. Methods Whole-body planar images and SPECT/CT images were acquired from 24 patients and 65 cycles at 24h, 48h, and >= 96h after administration of a mean activity of 6.4 GBq [Lu-177]Lu-PSMA-617 (range 3-10.9 GBq). Dosimetry was performed by use of the following approaches: 2D planar-based dosimetry, 3D SPECT/CT-based dosimetry, and hybrid dosimetry combining 2D and 3D data. Absorbed doses were calculated according to IDAC 2.1 for the kidneys, the liver, the salivary glands, and bone metastases. Results Mean absorbed doses estimated by 3D dosimetry (the reference method) were 0.54 +/- 0.28 Gy/GBq for the kidneys, 0.10 +/- 0.05 Gy/GBq for the liver, 0.81 +/- 0.34 Gy/GBq for the parotid gland, 0.72 +/- 0.39 Gy/GBq for the submandibular gland, and 1.68 +/- 1.32 Gy/GBq for bone metastases. Absorbed doses of normal organs estimated by hybrid dosimetry showed small, non-significant differences (median up to 4.0%) to the results of 3D dosimetry. Using 2D dosimetry, in contrast, significant differences (median up to 10.9%) were observed. Regarding bone metastases, small, but significant differences (median up to 7.0%) of absorbed dose were found for both, 2D dosimetry and hybrid dosimetry. Bland-Altman analysis revealed high agreement between hybrid dosimetry and 3D dosimetry for normal organs and bone metastases, but substantial differences between 2D dosimetry and 3D dosimetry. Conclusion Hybrid dosimetry provides high accuracy in estimation of absorbed dose in comparison to 3D dosimetry for all important organs and is therefore feasible for use in individualized PSMA-RLT.