Steiner Joseph, Nguyen Brandon, Jafari Farhad
Department of Radiology, University of Chicago, Chicago, IL, USA.
Department of Radiology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Mol Imaging. 2024 Nov 3;23:15353508241280015. doi: 10.1177/15353508241280015. eCollection 2024 Jan-Dec.
Radiopharmaceutical therapy (RPT) dosimetry can be challenging to perform due to sparse data measurements and variations in how the time activity curve (TAC) is determined. In this work, a single system of equations was theoretically derived to estimate the TAC.
A pharmacokinetic (PK) model was developed to estimate patient specific rate constants for a given set of body compartments. The PK model and an optimizer were numerically implemented to determine the rate constants and, using these physiologic data, to generate TACs and time integrated activities (TIAs) for 3 tissue systems from clinical data gathered in 5 patients. A fourth (aggregate) tissue compartment is added using conservation of activity considerations.
Feasibility of the PK model was demonstrated by successfully generating TACs and TIAs for all patients in a manner comparable to existing methods in the literature. The data are compared to smaller sampling regimes. Differences between the 3- and 4-compartment models show that conservation of activity considerations should be part of TAC estimations.
The results here suggest a new paradigm in RPT in using the rate constants so identified as a diagnostic tool and as a vehicle to achieving individualized tumorcidal dose and/or the maximum tolerable dose to normal tissues.
由于数据测量稀疏以及时间-活度曲线（TAC）确定方式的差异，放射性药物治疗（RPT）剂量测定颇具挑战性。在本研究中，从理论上推导了一个单一方程组来估计TAC。
建立了一个药代动力学（PK）模型，以估计给定身体隔室组的患者特异性速率常数。对PK模型和优化器进行了数值实现，以确定速率常数，并利用这些生理数据，根据5例患者收集的临床数据生成3个组织系统的TAC和时间积分活度（TIA）。通过考虑活度守恒增加了第四个（总合）组织隔室。
通过以与文献中现有方法相当的方式成功为所有患者生成TAC和TIA，证明了PK模型的可行性。将数据与较小的采样方案进行了比较。三室模型和四室模型之间的差异表明，活度守恒考虑应成为TAC估计的一部分。
此处结果表明RPT的一种新范式，即使用如此确定的速率常数作为诊断工具，并作为实现个体化肿瘤杀伤剂量和/或正常组织最大耐受剂量的手段。
