血管化实体瘤中 $^{18}$F-氟米索硝唑（$^{18}$F-FMISO）放射性药物输运的数学建模
Mathematical Modeling of $^{18}$F-Fluoromisonidazole ($^{18}$F-FMISO) Radiopharmaceutical Transport in Vascularized Solid Tumors
AI总结：
本研究通过时空多尺度数学建模，揭示了不同血管生成水平下 $^{18}$F-FMISO 在实体瘤内的输运规律，发现高微血管密度和扩散机制主导药物摄取，为肿瘤乏氧成像和临床决策提供理论依据。
摘要：
$^{18}$F-氟米索硝唑（$^{18}$F-FMISO）是一种极具前景的正电子发射断层扫描放射性药物，用于识别实体瘤中的乏氧区域。本研究采用时空多尺度数学建模，探讨不同水平的血管生成如何影响放射性药物在肿瘤内的输运。研究中使用了两种肿瘤几何结构，分别具有异质性和均匀分布的毛细血管网络，以纳入不同程度的微血管密度。异质性血管化肿瘤的合成图像通过模拟血管生成过程生成。所提出的多尺度时空模型考虑了肿瘤微环境中复杂的生理和生化因素，例如放射性药物制剂的跨血管输运、其通过扩散和对流机制进入间质空间的运动，以及最终被肿瘤细胞摄取的过程。结果表明，$^{18}$F-FMISO 摄取的定量和半定量指标在肿瘤生长的不同阶段在空间和时间上存在差异。均匀血管化肿瘤中存在的高微血管密度增加了细胞摄取，因为它允许放射性药物分子更有效地释放和快速分布。与异质性血管化肿瘤相比，这导致了摄取的增强。在肿瘤中微血管的异质性和均匀分布两种情况下，扩散输运机制都比对流更为显著。本研究的发现揭示了 $^{18}$F-FMISO 放射性药物分布及其在肿瘤微环境中递送背后的输运现象，有助于肿瘤科医生的日常决策过程。
英文摘要：
$^{18}$F-Fluoromisonidazole ($^{18}$F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of $^{18}$F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind $^{18}$F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes.
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