Patients with metastatic, castration-resistant prostate cancer (mCRPC) present with an increased tumor burden in the skeleton. For these patients, Lutetium-177 (Lu-177) radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has gained increasing interest with promising outcome data. Patient-individualized dosimetry enables quantification of therapy success with the aim of minimizing absorbed dose to organs at risk while maximizing absorbed dose to tumors. Different dosimetric approaches with varying complexity and accuracy exist for this purpose. The relatively simple OLINDA method applied to tumors assumes a homogeneous activity distribution in a sphere with unit density. Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density correction has the potential to overcome the assumption of homogeneous density in OLINDA and VSV methods, which could be a major limitation for the application in bone metastases with heterogeneous density. The aim of this investigation is a comparison of these methods for bone lesion dosimetry in mCRPC patients receiving Lu-177-PSMA therapy.
In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage deviation (PD) of absorbed lesion doses compared to full MC was + 7 ± 13% (min: -60%; max: +47%) for the OLINDA unit density sphere model. With an applied CT-based density weighting to account for density differences in bone lesions, PD was − 15 ± 6% (min: -54%; max: -2%). For a soft tissue VSV approach, large PDs of + 16 ± 13% (min: -56%; max: +57%) were found; after voxel-wise density correction this was reduced to -5 ± 2% (min: -15%; max: -2%). The use of a combination of standard soft tissue and cortical bone VSVs showed deviations of -35 ± 8% (min: -76%; max: +5%). With additional voxel-wise density weighting, the PD was − 3 ± 2% (min: -13%; max: 0%).
Based on our bone lesion dosimetry results, a VSV approach with subsequent CT-based, voxel-wise density correction enabled dose estimates, that closely replicate computationally-demanding gold-standard full MC dose simulations.