Section for Biomedical Physics, University Hospital for Radiation Oncology, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Phys Med Biol. 2012 Mar 21;57(6):1675-84. doi: 10.1088/0031-9155/57/6/1675. Epub 2012 Mar 7.
Tumour hypoxia can be assessed by positron emission tomography (PET) using radiotracers like [(18)F]fluoromisonidazole (Fmiso). The purpose of this work was to independently investigate the influence of chronic and acute hypoxia on the retention of Fmiso on the microscale. This was approached by modelling and simulating tissue oxygenation and Fmiso dynamics on the microscale based on tumour histology. Diffusion of oxygen and Fmiso molecules in tissue- and oxygen-dependent Fmiso binding were included in the model. Moreover, a model of fluctuating vascular oxygen tension was incorporated to theoretically predict the effects of acute hypoxia. Simulated tissue oxygen tensions (PO(2)) are strongly influenced by the modelled periodical fluctuations (period 40 min, total amplitude 10 mmHg and mean 35 mmHg). Fluctuations led to variations in mean PO(2) of up to 41% and in the hypoxic fraction (PO(2) < 5 mmHg) from 56% up to 65%. Significant Fmiso retention is caused by chronic (87%) as well as acute hypoxia (13%). By simulating Fmiso injection during different phases of the vascular PO(2) fluctuation cycle, it was found that acute hypoxia of an empirically valid magnitude does not influence the reproducibility of PET imaging. Thus, it may be impossible to separate acute and chronic hypoxia from serial PET images.
肿瘤缺氧可以通过正电子发射断层扫描（PET）使用放射性示踪剂如[(18)F]氟米索硝唑（Fmiso）来评估。这项工作的目的是独立研究慢性和急性缺氧对 Fmiso 微尺度保留的影响。通过基于肿瘤组织学在微尺度上对组织氧合和 Fmiso 动力学进行建模和模拟来实现这一目标。该模型包括了组织和氧依赖性 Fmiso 结合的氧气和 Fmiso 分子的扩散。此外，还纳入了波动血管氧张力模型来理论预测急性缺氧的影响。模拟的组织氧分压（PO2）强烈受到模型周期性波动的影响（周期 40 分钟，总幅度 10 毫米汞柱，平均 35 毫米汞柱）。波动导致平均 PO2 变化高达 41%，缺氧分数（PO2 < 5 毫米汞柱）从 56%增加到 65%。慢性（87%）和急性缺氧（13%）都会导致 Fmiso 的显著保留。通过模拟在血管 PO2 波动周期的不同阶段进行 Fmiso 注射，发现急性缺氧的实际有效幅度不会影响 PET 成像的可重复性。因此，从连续的 PET 图像中可能无法区分急性和慢性缺氧。
