Williams M V, Denekamp J, Minchinton A I, Stratford M R
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):477-81. doi: 10.1016/0360-3016(82)90665-4.
The radiosensitizing efficiency of a novel 2-nitroimidazole (Ro 03-8799) has been compared with that of misonidazole. Each compound was assessed by constructing dose response curves for regrowth delay using a range of drug doses. The concentration of each compound was measured in tumor homogenates with high performance liquid chromatography (HPLC). When compared on the basis of administered dose the new compound was no more efficient than misonidazole. Comparison on the basis of measured tumor concentrations showed that Ro 03-8799 was 3--4 times more efficient than misonidazole, but only at very high drug levels. Previous in vitro studies had shown a constant 10-fold difference in potency. In order to eliminate possible artifacts caused by the short half life in mice, repeated injections of Ro 03-8799 were used to maintain a constant tumor concentration for two hours before irradiation. No increase in effectiveness was observed with prolonged exposure. This is a charged compound whose distribution is pH dependent; gross tumor levels should therefore be interpreted with caution.
一种新型2-硝基咪唑（Ro 03-8799）的放射增敏效率已与米索硝唑的放射增敏效率进行了比较。通过使用一系列药物剂量构建再生长延迟的剂量反应曲线来评估每种化合物。用高效液相色谱法（HPLC）测量肿瘤匀浆中每种化合物的浓度。基于给药剂量进行比较时，新化合物并不比米索硝唑更有效。基于测量的肿瘤浓度进行比较表明，Ro 03-8799的效率比米索硝唑高3至4倍，但仅在非常高的药物水平下如此。先前的体外研究表明其效力存在恒定的10倍差异。为了消除小鼠体内半衰期短可能导致的假象，在照射前重复注射Ro 03-8799以维持肿瘤浓度恒定两小时。长时间暴露未观察到有效性增加。这是一种带电荷的化合物，其分布取决于pH值；因此，对肿瘤总体水平的解读应谨慎。
