Casciari J J, Graham M M, Rasey J S
Department of Radiation Oncology, University of Washington Medical Center, Seattle 91895, USA.
Med Phys. 1995 Jul;22(7):1127-39. doi: 10.1118/1.597506.
[F-18]fluoromisonidazole (FMISO), a positron-emitting nitroimidazole, binds preferentially to hypoxic cells. It has been used to image hypoxia in human tumors with positron emission tomography (PET). In order to quantify tumor oxygenation status from these PET data, a kinetic model of FMISO cellular bioreduction has been developed to relate cellular oxygen concentration to the cellular FMISO reaction rate constant, kappa A. Also, a compartmental model of FMISO transport and metabolism has been developed to compute the volume average kappa A in tissue regions from [F-18]FMISO PET time-activity data. This compartmental model was characterized using Monte Carlo simulations and [F-18]FMISO PET time-activity data. The model performed well in Monte Carlo simulations; performance was enhanced by fixing three of the seven model parameters at physiologically reasonable values. The four parameters optimized were blood flow rate, kappa A for two partial volume/spillover correction factors. The model was able to accurately determine kappa A for a variety of computer-generated time-activity curv including those for hypothetical heterogeneous tissue regions and poorly perfused tissue regions. The model was also able to fit [H-3]FMISO time-activity data from 36B-10 rat tumors as well as [F-18]FMISO PET time-activity data from a human patient with a base of the tongue squamous cell carcinoma. The kappa A values in muscles ROIs were comparable to those in well-oxygenated cell monolayers while kappa A values in tumor ROIs were greater, suggesting the presence of hypoxic cells in the tumor.
[F-18]氟米索硝唑（FMISO）是一种正电子发射型硝基咪唑，优先与缺氧细胞结合。它已被用于通过正电子发射断层扫描（PET）对人类肿瘤中的缺氧情况进行成像。为了从这些PET数据中量化肿瘤氧合状态，已开发出FMISO细胞生物还原动力学模型，以将细胞氧浓度与细胞FMISO反应速率常数κA相关联。此外，还开发了FMISO转运和代谢的房室模型，以根据[F-18]FMISO PET时间-活度数据计算组织区域中的体积平均κA。该房室模型通过蒙特卡罗模拟和[F-18]FMISO PET时间-活度数据进行了表征。该模型在蒙特卡罗模拟中表现良好；通过将七个模型参数中的三个固定在生理合理值，性能得到了提高。优化的四个参数是血流速率、两个部分体积/溢出校正因子的κA。该模型能够准确确定各种计算机生成的时间-活度曲线的κA，包括那些假设的异质组织区域和灌注不良组织区域的曲线。该模型还能够拟合来自36B-10大鼠肿瘤的[H-3]FMISO时间-活度数据以及来自一名舌底鳞状细胞癌患者的[F-18]FMISO PET时间-活度数据。肌肉感兴趣区域（ROI）中的κA值与氧合良好的细胞单层中的κA值相当，而肿瘤ROI中的κA值更大，表明肿瘤中存在缺氧细胞。
