DETERMINATION OF THE RADIOBIOLOGICALLY HYPOXIC FRACTION IN MULTICELLULAR SPHEROIDS FROM DATA ON THE UPTAKE OF [H-3] FLUOROMISONIDAZOLE
DETERMINATION OF THE RADIOBIOLOGICALLY HYPOXIC FRACTION IN MULTICELLULAR SPHEROIDS FROM DATA ON THE UPTAKE OF [H-3] FLUOROMISONIDAZOLE
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DOI：
10.2307/3579086
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发表时间：
1995-01-01
影响因子：
3.4
通讯作者：
RASEY, JS
中科院分区：
文献类型：
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作者：
CASCIARI, JJ;RASEY, JS
氟咪唑[1-（2-硝基咪唑基）-2-羟基-3-氟-丙烷，FMISO]显示出作为缺氧显像剂的前景：它在体外优先结合单层缺氧细胞，并在体内放射生物学缺氧肿瘤中蓄积。使用多细胞球体模型来确定是否可以从FMISO摄取数据预测放射生物学低氧分数。将直径约为500 μ m的中国仓鼠V79- 171 b球状体在有氧（空气中5%CO2）、低氧（5%CO2，5%O-2，N-2）或缺氧（5%CO2，N-2）条件下暴露于50 mM [H-3]FMISO 1至6小时，并测量FMISO摄取。缺氧球体中的摄取与缺氧细胞单层中的摄取相似，而有氧球体中几乎没有摄取。建立了一个数学模型，从FMISO摄取数据计算乏氧球体中放射生物乏氧分数。获得了15%的放射生物学低氧分数，与从辐射存活测定（17%）和耗氧量测量（22%）确定的一致。我们得出结论，FMISO吸收率V79- 171 b球体与放射生物学缺氧分数。此外，如果已知给定肿瘤细胞类型的FMISO摄取对氧浓度的依赖性，则可以从FMISO摄取的数据计算放射生物学低氧分数。
Fluoromisonidazole [1-(2-nitroimidazolyl)-2-hydroxy-3-fluoro-propane, FMISO] shows promise as a hypoxia imaging agent: it binds preferentially to anoxic cells in monolayers in vitro and accumulates in radiobiologically hypoxic tumors in vivo. The multicellular spheroid model was used to determine if the radiobiologically hypoxic fraction could be predicted from data on the uptake of FMISO. Chinese hamster V79-171b spheroids approximately 500 mu m in diameter were exposed to 50 mM [H-3]FMISO for 1 to 6 h under aerobic (5% CO2 in air), hypoxic (5% CO2, 5% O-2, in N-2) or anoxic (5% CO2 in N-2) conditions and FMISO uptake was measured. Uptake in anoxic spheroids was similar to that in anoxic cell monolayers, while there was virtually no uptake in aerobic spheroids. A mathematical model was developed to calculate the radiobiologically hypoxic fraction in the hypoxic spheroids from the data on FMISO uptake. A radiobiologically hypoxic fraction of 15% was obtained, consistent with that determined from radiation survival assays (17%) and measurements of oxygen consumption (22%). We conclude that the rate of FMISO uptake in V79-171b spheroids correlates with the radiobiologically hypoxic fraction. Furthermore, the radiobiologically hypoxic fraction can be calculated from data on FMISO uptake if the dependence of FMISO uptake on oxygen concentration is known for a given tumor cell type.