Joint Department of Physics, Royal Marsden NHSFT, Sutton, United Kingdom; The Institute of Cancer Research, London, United Kingdom; Medical Physics and Clinical Engineering, St. George's University Hospital NHSFT, London, United Kingdom.
Joint Department of Physics, Royal Marsden NHSFT, Sutton, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):884-892. doi: 10.1016/j.ijrobp.2019.07.022. Epub 2019 Jul 23.
Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for Ra-Dichloride in patients to improve understanding of the underlying mechanisms.
A compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg Ra-Dichloride) for plasma, bone surfaces, small intestines, large intestines, and excretion data. Rate constants were extracted. Rate constant variability between patients and treatments was assessed. A population model was proposed and compared with the established International Commission on Radiological Protection-67 compartmental model.
A single bone compartment cannot accurately describe activity retention in the skeleton. The addition of a second bone compartment improved the fit to skeleton retention data, and the Akaike information criterion decreased. Mean rate constants of 4.0 (range, 1.9-10.9) and 0.15 (0.07-0.39) h were obtained for transport from plasma to first bone compartment and vice versa. Rate constants from first to second bone compartment and back of 0.03 (0.02-0.06) and 0.008 (0.003-0.011) h were calculated. Rate constants for individual patients showed no significant difference between patients and treatments.
The developed compartmental model suggests that Ra-Dichloride initially locates at the bone surface and is then incorporated into the bone matrix relatively quickly. This observation could have implications for dosimetry and understanding of the effects of alpha radiation on normal bone tissue. Results suggest that a population model based on patient measurements is feasible.
镭-二氯化物用于治疗去势抵抗性前列腺癌转移骨病患者。镭-二氯化物的摄取和作用机制尚不清楚。本研究旨在开发一种镭-二氯化物在患者体内的房室模型，以加深对潜在机制的理解。
基于 6 名患者（2 次接受 110 kBq/kg 镭-二氯化物治疗）的血浆、骨表面、小肠、大肠和排泄数据，建立了一个房室模型。提取速率常数。评估了患者和治疗之间的速率常数变异性。提出了一个群体模型，并与国际辐射防护委员会第 67 号房室模型进行了比较。
单一的骨室不能准确描述骨骼中放射性的保留。增加第二个骨室可以改善对骨骼保留数据的拟合，Akaike 信息准则降低。从血浆到第一骨室和反之的转运的平均速率常数分别为 4.0（范围，1.9-10.9）和 0.15（0.07-0.39）h。从第一骨室到第二骨室和返回的速率常数分别为 0.03（0.02-0.06）和 0.008（0.003-0.011）h。个体患者的速率常数在患者和治疗之间没有显著差异。
所开发的房室模型表明，镭-二氯化物最初位于骨表面，然后相对较快地被纳入骨基质。这一观察结果可能对剂量学和理解α辐射对正常骨组织的影响有影响。结果表明，基于患者测量的群体模型是可行的。
