The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model selection (PBMS) in a large population for ¹⁷⁷Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean ± SD) of [¹⁷⁷Lu]Lu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.8 h), 2 (18.7 ± 0.9 h), 3 (42.6 ± 1.0 h), 4 (66.3 ± 0.9 h), and 5 (160.3 ± 24.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function’s parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods. Results: The function $${A}_{1} {e}^{-\left({\hbox{ \lambda }}_{1}+{\hbox{ \lambda }}_{\hbox{ phys }}\right)t}+{A}_{2} {e}^{-\left({\hbox{ \lambda }}_{2}+{\hbox{ \lambda }}_{\hbox{ phys }}\right)t}-{A}_{3} {e}^{-\left({\hbox{ \lambda }}_{3}+{\hbox{ \lambda }}_{\hbox{ phys }}\right)t}-\left({A}_{1}+{A}_{2}-{A}_{3}\right){e}^{-\left({\hbox{ \lambda }}_{\hbox{ bc }}+{\hbox{ \lambda }}_{\hbox{ phys }}\right)t}$$ was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.6 ± 1.0 h) showed a relatively low mean RD of –4.4% ± 9.4% and median RD of –0.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1–5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points. Conclusion: Our results show that a single measurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLME method and PBMS.

本研究的目的是研究使用 SPECT/CT 数据、非线性混合效应 (NLME) 模型和基于人群的模型选择 (PBMS) 的单时间点 (STP) 肾剂量测定成像的准确性。大量人群进行¹⁷⁷ Lu标记的前列腺特异性膜抗原治疗。方法： [ ¹⁷⁷ Lu]Lu-PSMA-617 在时间点 1 (1.8 ± 0.8 h)、2 (18.7 ± 0.9 h)、3 (42.6 ± 1.0 h)、4 (使用 SPECT/CT 从 63 名转移性去势抵抗性前列腺癌患者中获得注射后 66.3 ± 0.9 h) 和 5 (160.3 ± 24.2 h) 的样本。十三个函数是从 1 到 5 指数函数的各种参数化导出的。该函数的参数在 NLME 框架中适合所有时间点 (ATP) 数据。 PBMS NLME 方法使用拟合优度检验和 Akaike 权重来选择拟合数据的最佳函数。 ATP 拟合的最佳函数用于计算参考时间积分活性和吸收剂量。在STP剂量测定中，将具有STP数据的特定患者的参数同时拟合到该患者不同时间点的STP数据和所有其他患者的ATP数据。 STP 拟合的参数用于计算 STP 时间积分活性和吸收剂量。使用相对偏差 (RD) 和均方根误差 (RMSE) 来分析计算出的 STP 吸收剂量与从最佳拟合 ATP 函数获得的参考吸收剂量相比的准确性。将使用 PBMS NLME 建模的 STP 剂量测定性能与 Hänscheid 和 Madsen 方法进行了比较。结果：函数$${A}_{1} {e}^{-\left({\hbox{ \lambda }}_{1}+{\hbox{ \lambda }}_{\hbox{ phys }}\right) t}+{A}_{2} {e}^{-\left({\hbox{ \lambda }}_{2}+{\hbox{ \lambda }}_{\hbox{ phys }}\right )t}-{A}_{3} {e}^{-\left({\hbox{ \lambda }}_{3}+{\hbox{ \lambda }}_{\hbox{ phys }}\右)t}-\left({A}_{1}+{A}_{2}-{A}_{3}\right){e}^{-\left({\hbox{ \lambda } }_{\hbox{ bc }}+{\hbox{ \lambda }}_{\hbox{ phys }}\right)t}$$被选为最佳拟合 ATP 函数，Akaike 权重为 100%。对于 STP 剂量测定，在时间点 3（42.6 ± 1.0 小时）通过 SPECT/CT 进行的 STP 测量显示相对较低的平均 RD 为 –4.4% ± 9.4%，中位 RD 为 –0.7%。与其他 4 个时间点相比，时间点 3 的 RMSE 值最低。时间点 1-5 的吸收剂量 RD 的 RMSE 分别为 23%、16%、10%、20% 和 53%。在所有研究时间点上，使用 PBMS NLME 方法进行的 STP 剂量测定均优于 Hänscheid 和 Madsen 方法。结论：我们的结果表明，注射后 2 d 进行 SPECT/CT 的单次测量可用于使用 NLME 方法和 PBMS 计算准确的肾脏吸收剂量。