使用正电子发射断层扫描（PET）和药代动力学模型进行放射性核素治疗的时间积分活度系数估计：关于采样计划和噪声影响的模拟研究
Time-integrated activity coefficient estimation for radionuclide therapy using PET and a pharmacokinetic model: A simulation study on the effect of sampling schedule and noise.
作者信息
Hardiansyah Deni, Guo Wei, Kletting Peter, Mottaghy Felix M, Glatting Gerhard
机构信息
Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany and Department of Radiation Oncology, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany.
Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany.
出版信息
Med Phys. 2016 Sep;43(9):5145. doi: 10.1118/1.4961012.
PURPOSE
The aim of this study was to investigate the accuracy of PET-based treatment planning for predicting the time-integrated activity coefficients (TIACs).
METHODS
The parameters of a physiologically based pharmacokinetic (PBPK) model were fitted to the biokinetic data of 15 patients to derive assumed true parameters and were used to construct true mathematical patient phantoms (MPPs). Biokinetics of 150 MBq (68)Ga-DOTATATE-PET was simulated with different noise levels [fractional standard deviation (FSD) 10%, 1%, 0.1%, and 0.01%], and seven combinations of measurements at 30 min, 1 h, and 4 h p.i. PBPK model parameters were fitted to the simulated noisy PET data using population-based Bayesian parameters to construct predicted MPPs. Therapy simulations were performed as 30 min infusion of (90)Y-DOTATATE of 3.3 GBq in both true and predicted MPPs. Prediction accuracy was then calculated as relative variability vorgan between TIACs from both MPPs.
RESULTS
Large variability values of one time-point protocols [e.g., FSD = 1%, 240 min p.i., vkidneys = (9 ± 6)%, and vtumor = (27 ± 26)%] show inaccurate prediction. Accurate TIAC prediction of the kidneys was obtained for the case of two measurements (1 and 4 h p.i.), e.g., FSD = 1%, vkidneys = (7 ± 3)%, and vtumor = (22 ± 10)%, or three measurements, e.g., FSD = 1%, vkidneys = (7 ± 3)%, and vtumor = (22 ± 9)%.
CONCLUSIONS
(68)Ga-DOTATATE-PET measurements could possibly be used to predict the TIACs of (90)Y-DOTATATE when using a PBPK model and population-based Bayesian parameters. The two time-point measurement at 1 and 4 h p.i. with a noise up to FSD = 1% allows an accurate prediction of the TIACs in kidneys.
目的
本研究旨在探讨基于正电子发射断层扫描（PET）的治疗计划在预测时间积分活度系数（TIACs）方面的准确性。
方法
将基于生理的药代动力学（PBPK）模型的参数拟合到15名患者的生物动力学数据中，以得出假定的真实参数，并用于构建真实的数学患者体模（MPPs）。使用不同的噪声水平[分数标准偏差（FSD）10%、1%、0.1%和0.01%]模拟150 MBq （68）Ga-DOTATATE-PET的生物动力学，并在注射后30分钟、1小时和4小时进行七种测量组合。使用基于群体的贝叶斯参数将PBPK模型参数拟合到模拟的噪声PET数据中，以构建预测的MPPs。在真实和预测的MPPs中，均进行了3.3 GBq （90）Y-DOTATATE的30分钟输注的治疗模拟。然后将预测准确性计算为两个MPPs的TIACs之间的相对变异性vorgan。
结果
单时间点方案的变异性值较大[例如，FSD = 1%，注射后240分钟，v肾脏 = （9 ± 6）%，v肿瘤 = （27 ± 26）%]，表明预测不准确。对于两次测量（注射后1小时和4小时）的情况，例如FSD = 1%，v肾脏 = （7 ± 3）%，v肿瘤 = （22 ± 10）%，或三次测量，例如FSD = 1%，v肾脏 = （7 ± 3）%，v肿瘤 = （22 ± 9）%，可以获得对肾脏TIAC的准确预测。
结论
当使用PBPK模型和基于群体的贝叶斯参数时，（68）Ga-DOTATATE-PET测量可能可用于预测（90）Y-DOTATATE的TIACs。注射后1小时和4小时的两个时间点测量，噪声高达FSD = 1%，可以准确预测肾脏中的TIACs。
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