Individualized dosimetry is recommended for [177Lu]Lu-PSMA radioligand therapy (RLT) which is resource-intensive and protocols are often not optimized. Therefore, a simulation study was performed focusing on the determination of efficient optimal sampling schedules (OSS) for renal and tumour dosimetry by investigating different numbers of time points (TPs). Sampling schedules with 1–4 TPs were investigated. Time-activity curves of the kidneys and two tumour lesions were generated based on a physiologically based pharmacokinetic (PBPK) model and biokinetic data of 13 patients who have undergone [177Lu]Lu-PSMA I&T therapy. Systematic and stochastic noise of different ratios was considered when modelling time-activity data sets. Time-integrated activity coefficients (TIACs) were estimated by simulating the hybrid planar/SPECT method for schedules comprising at least two TPs. TIACs based on one single SPECT/CT measurement were estimated using an approximation for reducing the number of fitted parameters. For each sampling schedule, the root-mean-squared error (RMSE) of the deviations of the simulated TIACs from the ground truths for 1000 replications was used as a measure for accuracy and precision. All determined OSS included a late measurement at 192 h p.i., which was necessary for accurate and precise tumour TIACs. OSS with three TPs were identified to be 3–4, 96–100 and 192 h with an additional SPECT/CT measurement at the penultimate TP. Kidney and tumour RMSE of 6.4 to 7.7% and 6.3 to 7.8% were obtained, respectively. Shortening the total time for dosimetry to e.g. 96 h resulted in kidney and tumour RMSE of 6.8 to 8.3% and 9.1 to 11%, respectively. OSS with four TPs showed similar results as with three TPs. Planar images at 4 and 68 h and a SPECT/CT shortly after the 68 h measurement led to kidney and tumour RMSE of 8.4 to 12% and 12 to 16%, respectively. One single SPECT/CT measurement at 52 h yielded good approximations for the kidney TIACs (RMSE of 7.0%), but led to biased tumour TIACs. OSS allow improvements in accuracy and precision of renal and tumour dosimetry for [177Lu]Lu-PSMA therapy with potentially less effort. A late TP is important regarding accurate tumour TIACs.

中文翻译：

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采样时间表对[177Lu] Lu-PSMA剂量测定的影响。

建议对[177Lu] Lu-PSMA放射配体疗法（RLT）进行个体化的剂量测定，这是资源密集型的，而且协议通常没有优化。因此，进行了一项模拟研究，重点是通过调查不同数量的时间点（TP）来确定肾脏和肿瘤剂量测定的有效最佳采样时间表（OSS）。研究了具有1-4个TP的采样计划。基于生理学药代动力学（PBPK）模型和13位接受[177Lu] Lu-PSMA I＆T治疗的患者的生物动力学数据，生成了肾脏和两个肿瘤病变的时间活动曲线。对时间活动数据集进行建模时，应考虑不同比率的系统噪声和随机噪声。通过模拟包含至少两个TP的计划的混合平面/ SPECT方法，可以估计时间积分活动系数（TIAC）。使用近似值来估计基于单个SPECT / CT测量的TIAC，以减少拟合参数的数量。对于每个采样计划，将1000次重复的模拟TIAC与地面实况的偏差的均方根误差（RMSE）用作准确性和精确度的量度。所有确定的OSS都包括在pi 192 h的延迟测量，这对于准确而精确的肿瘤TIAC是必需的。带有三个TP的OSS被确定为3–4、96–100和192 h，并在倒数第二个TP处进行了额外的SPECT / CT测量。肾脏和肿瘤的RMSE分别为6.4％至7.7％和6.3％至7.8％。将剂量测定的总时间缩短到例如 96 h导致肾脏和肿瘤的RMSE分别为6.8％至8.3％和9.1％至11％。具有四个TP的OSS显示的结果与三个TP相似。测量68 h后不久在4和68 h的平面图像和SPECT / CT分别导致肾脏和肿瘤的RMSE分别为8.4％至12％和12％至16％。在52 h时进行一次SPECT / CT测量可获得肾脏TIAC的良好近似值（RMSE为7.0％），但导致了肿瘤TIAC的偏倚。OSS可以以更少的精力来提高[177Lu] Lu-PSMA治疗的肾脏和肿瘤剂量测定的准确性和精确度。对于准确的肿瘤TIAC，晚期TP很重要。测量68 h后不久在4和68 h的平面图像和SPECT / CT分别导致肾脏和肿瘤的RMSE分别为8.4％至12％和12％至16％。在52 h进行一次单次SPECT / CT测量可得出肾脏TIAC的良好近似值（RMSE为7.0％），但导致肿瘤TIAC偏倚。OSS可以以更少的精力来提高[177Lu] Lu-PSMA治疗的肾脏和肿瘤剂量测定的准确性和精确度。对于准确的肿瘤TIAC，晚期TP很重要。测量68 h后不久在4和68 h的平面图像和SPECT / CT分别导致肾脏和肿瘤的RMSE分别为8.4％至12％和12％至16％。在52 h时进行一次SPECT / CT测量可获得肾脏TIAC的良好近似值（RMSE为7.0％），但导致了肿瘤TIAC的偏倚。OSS可以以更少的精力来提高[177Lu] Lu-PSMA治疗的肾脏和肿瘤剂量测定的准确性和精确度。对于准确的肿瘤TIAC，晚期TP很重要。