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. 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%). 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.

中文翻译：

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剂量学方法对 PSMA 治疗中骨病变吸收剂量估计的影响：适用于接受 Lu-177-PSMA-I&T 的 mCRPC 患者

患有转移性去势抵抗性前列腺癌 (mCRPC) 的患者骨骼中的肿瘤负荷增加。对于这些患者，针对前列腺特异性膜抗原 (PSMA) 的 Lutetium-177 (Lu-177) 放射配体疗法获得了越来越多的兴趣，并获得了有希望的结果数据。患者个体化剂量测定能够提高治疗成功率，目的是最大限度地减少风险器官的吸收剂量，同时最大限度地提高肿瘤的吸收剂量。为此，存在具有不同复杂性和准确性的不同剂量测定方法。应用于肿瘤的医疗内辐射剂量 (MIRD) 形式假设在具有单位密度的球体中具有均匀的活性分布，用于推导肿瘤 S 值 (TSV)。体素 S 值 (VSV) 方法可以解释异质活动，但针对特定组织进行模拟。完整的患者个体蒙特卡罗 (MC) 吸收剂量模拟解决了异质活动和密度分布。随后的基于 CT 的密度加权有可能用 TSV 和 VSV 方法克服 MIRD 形式中均匀密度的假设，这可能是在具有不均匀密度的骨转移中应用的主要限制。本研究的目的是比较这些方法在接受 Lu-177-PSMA 治疗的 mCRPC 患者中进行骨病变剂量测定。总共分析了 15 名 mCRPC 患者的 289 处骨病变。与 MC 相比，每个病灶的平均吸收剂量的百分比差异 (PD)，在所有病灶上取平均值，对于 TSV 为 + 14 ± 10%（最小值：- 21%；最大值：+ 56%）。通过对患者 CT 图像使用 Hounsfield 单位 (HU) 到密度转换的病灶个体密度加权，PD 降低至 − 8 ± 1%（最小值： − 10%；最大值： − 3%）。三维 (3D) 体素剂量测定方法的体素水平上的 PD，平均每个病变，显示软组织 VSV 方法的大 PD 为 + 18 ± 11%（最小值：- 27%；最大值：+ 58%）与MC相比；在逐体素密度校正后，这减少到 - 5 ± 1%（最小值：- 12%；最大值：- 2%）。患者个体 MC 吸收剂量模拟能够解释骨病变中的不均匀密度。由于计算工作妨碍了其常规临床应用，因此使用 TSV 或 VSV 剂量测定方法。该研究表明，在 Lu-177-PSMA 治疗骨病变剂量测定中，对 TSV 或 VSV 进行病变个体密度加权的必要性。