Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T

Abstract

Background 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 improvement 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 Medical Internal Radiation Dose (MIRD) formalism applied to tumors assumes a homogeneous activity distribution in a sphere with unit density for derivation of tumor S values (TSV). Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) absorbed dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density weighting has the potential to overcome the assumption of homogeneous density in the MIRD formalism with TSV 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. Results In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage difference (PD) of average absorbed dose per lesion compared to MC, averaged over all lesions, was + 14 ± 10% (min: − 21%; max: + 56%) for TSVs. With lesion-individual density weighting using Hounsfield Unit (HU)-to-density conversion on the patient’s CT image, PD was reduced to − 8 ± 1% (min: − 10%; max: − 3%). PD on a voxel level for three-dimensional (3D) voxel-wise dosimetry methods, averaged per lesion, revealed large PDs of + 18 ± 11% (min: − 27%; max: + 58%) for a soft tissue VSV approach compared to MC; after voxel-wise density correction, this was reduced to − 5 ± 1% (min: − 12%; max: − 2%). Conclusion Patient-individual MC absorbed dose simulation is capable to account for heterogeneous densities in bone lesions. Since the computational effort prevents its routine clinical application, TSV or VSV dosimetry approaches are used. This study showed the necessity of lesion-individual density weighting for TSV or VSV in Lu-177-PSMA therapy bone lesion dosimetry.

Dosimetry in Lu-177-PSMA-617 prostate-specific membrane antigen targeted radioligand therapy: a systematic review

“…This is likely due to the smaller size of the lacrimal gland. Previous studies have shown that interpatient variability, differences in methodologies, models used for dose assessment, imaging system calibration, time-activity curve fitting, variation in organ volumes, intra-individual size variation, 2D/3D dosimetry approach and the number of imaging time points post-therapy, all are known to induce variations in absorbed dose estimates [31,33,36,47,48,57,58]. The use of various dosimetry software and techniques are also leads to variation in absorbed dose estimates for organs and tissues [59,60].…”

“…The absorbed dose estimates for body organs and tumor lesions in 177 Lu-PSMA-617 SRT are generally performed using the medical internal radiation dose schema [40]. However, the accuracy of dose estimation can be improved by the use of more sophisticated voxel-based dosimetry methods which include inhomogeneous activity distribution in the area of interest, the actual size of an organ, multi-single photon emission computed tomography/computed tomography (SPECT/CT) images and simulation codes [36,41].…”

Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs

“…While this method is the most accurate, it is very computationally intensive and time consuming. Alternative approaches to full MC simulations are also being actively explored 33 .…”

Correction to: Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T

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Following publication of the original article [1], it was reported that due to a typesetting error some text was mistakenly introduced in the "MC method: Patient-specific Monte Carlo (MC) absorbed dose simulation" and "Comparison of dosimetry methods" subsections.The erroneous text is highlighted in bold in the below passages and has been removed in the original article.In the "MC method: Patient-specific Monte Carlo (MC) absorbed dose simulation" the affected sentence was:A CT scan of a Gammex tissue characterization phantom (Gammex 467; Gammex Inc., Middleton, WI) using the same imaging parameters from the patient scans was perfMC method: Patient-specificormed, which confirmed the HU-to-density relationship of our CT device with that implemented in GATE. GATE converts HU-to-density values with internal tables based on Schneider et al [22].The corrected sentence reads: A CT scan of a Gammex tissue characterization phantom (Gammex 467; Gammex Inc., Middleton, WI) using the same imaging parameters from the patient scans was performed, which confirmed the HU-to-density relationship of our CT device with that implemented in GATE.

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“…Following publication of the original article [1], it was reported that due to a typesetting error some text was mistakenly introduced in the "MC method: Patient-specific Monte Carlo (MC) absorbed dose simulation" and "Comparison of dosimetry methods" subsections.…”