Department of Radiology, University of Iowa, Iowa City, IA, 52242, USA.
Department of Endocrinology, University of Iowa, Iowa City, IA, 52242, USA.
Med Phys. 2018 May;45(5):2318-2324. doi: 10.1002/mp.12886. Epub 2018 Apr 16.
Although personalized dosimetry may be desirable for radionuclide therapy treatments, the multiple time samples required to determine the total integrated activity puts a burden on patients and clinic resources. The aim of this paper is to demonstrate that when some prior knowledge is known about the tracer kinetic parameters, the total integrated activity (and thus radiation dose) can be estimated from a single time sample.
Mathematical derivations have been performed to generate equations for the total integrated activity in terms of a single time sample of activity for monoexponential and biexponential clearance. Simulations were performed using both exponential models where the rate constants and associated parameters were randomly sampled from distributions with a known mean. The actual total integrated activity for each random sample was compared with the estimated total integrated activity using the mean value of the parameters. Retrospective analysis of Y DOTATOC data from a clinical trial provided a comparison of actual kidney dose with the estimated kidney dose using the single time point approach.
The optimal sampling time for the single point approach was found to be equal to the mean time of the rate constant. The simulation results for the monoexponential and biexpoential models were similar. Regressions comparing the actual and estimated total integrated activity had very high correlations (r > 0.95) along with acceptable standard errors of estimate, especially at the optimal sampling point. The retrospective analysis of the Y DOTATOC data also yielded similar results with an r = 0.95 and a standard error of estimate of 61 cGy.
In situations where there is prior knowledge about the population averages of kinetic parameters, these results suggest that the single time point approach can be used to estimate the total integrated activity and dose with sufficient accuracy to manage radionuclide therapy. This will make personalized dosimetry much easier to perform and more available to the community.
虽然放射性核素治疗可能需要个体化剂量，但确定总积分活度需要多次时间采样，这给患者和临床资源带来了负担。本文旨在证明，当对示踪剂动力学参数有一些先验知识时，可以从单个时间样本估计总积分活度（因此也可以估计辐射剂量）。
对单指数和双指数清除的单一时间样本活性的总积分活度进行了数学推导，以生成方程。使用指数模型进行了模拟，其中速率常数和相关参数是从具有已知平均值的分布中随机抽样的。使用参数的平均值将每个随机样本的实际总积分活度与估计的总积分活度进行比较。对来自临床试验的 Y DOTATOC 数据的回顾性分析比较了单点方法的实际肾脏剂量和估计的肾脏剂量。
发现单点方法的最佳采样时间等于速率常数的平均值。单指数和双指数模型的模拟结果相似。实际和估计的总积分活度之间的回归具有非常高的相关性（r ＞ 0.95），并且估计值的标准误差也可以接受，尤其是在最佳采样点。Y DOTATOC 数据的回顾性分析也得到了类似的结果，r = 0.95，估计值的标准误差为 61 cGy。
在具有群体动力学参数平均值先验知识的情况下，这些结果表明单点方法可用于以足够的精度估计总积分活度和剂量，从而更轻松地进行个体化剂量治疗，并使其在更广泛的范围内得到应用。
