Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor.
Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor.
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发表时间：
1987-06
期刊：
影响因子：
11.2
通讯作者：
B. Henderson;V. Fingar
中科院分区：
文献类型：
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作者：
B. Henderson;V. Fingar
采用RIF小鼠肿瘤模型，在体外和体内研究了肿瘤氧合与光动力治疗（PDT）效果的关系。测定了25 mg/kg卟啉（二血卟啉醚）在体内暴露、体外分离和光照的RIF细胞光动力失活的氧依赖性。在缺氧条件下，细胞未被杀死，在5% O2下达到完全效果，在1% O2下发现细胞失活的一半值。采用细胞放射敏感性体外克隆测定法评估对照和pdt治疗肿瘤在体内γ辐照后的肿瘤缺氧情况。体外对照实验证实，pdt存活的RIF细胞的放射敏感性与未处理的对照细胞相同。治疗大小的RIF肿瘤（80-120 mg）不含可检测到的缺氧肿瘤细胞组分。PDT治疗包括在630nm光照45 J/cm2前24小时内静脉注射10 mg/kg双血卟啉醚，在治疗时间10分钟内使约9%的肿瘤细胞严重缺氧。光照时间为30 min （135 J/cm2）时，缺氧肿瘤细胞比例为17%，在处理后1 h内增加到47%。尽管在PDT光治疗过程中会迅速诱导肿瘤缺氧，但在目前的治疗条件下（肿瘤区域脱毛，10 mg/kg双血卟啉醚，135 J/cm2），肿瘤的治愈率很高（81%）。考虑到低氧浓度下光动力杀死细胞的效果降低，PDT本身能快速诱导肿瘤缺氧，肿瘤治愈率高，我们必须得出结论，在RIF肿瘤中，缺氧肿瘤细胞的失活不是由直接的光动力细胞毒性机制引起的，因此不局限于PDT肿瘤反应。
The relationship between tumor oxygenation and the effectiveness of photodynamic therapy (PDT) was studied in vitro and in vivo using the RIF mouse tumor model. The oxygen dependence of photodynamic inactivation of RIF cells, which had been exposed to 25 mg/kg porphyrin (dihematoporphyrin ether) in vivo, isolated and illuminated in vitro, was determined. No cell kill was achieved under anoxic conditions, full effect was reached at 5% O2, and the half value of cell inactivation was found to be at 1% O2. Tumor hypoxia was assessed after in vivo gamma-irradiation of control and PDT-treated tumors by in vitro clonogenic assay of cell radiosensitivity. In vitro control experiments established that the radio-sensitivity of PDT-surviving RIF cells was identical to that of untreated control cells. RIF tumors of treatment size (80-120 mg) contained no detectable hypoxic tumor cell fraction. PDT treatment consisting of i.p. injection of 10 mg/kg dihematoporphyrin ether 24 h prior to 45 J/cm2 of 630 nm light, rendered approximately 9% of tumor cells severely hypoxic within 10 min of treatment time. An illumination period of 30 min (135 J/cm2) induced a hypoxic tumor cell fraction of 17%, which increased to 47% within 1 h posttreatment. Despite the prompt induction of tumor hypoxia during PDT light treatment, the tumors proved highly curable (81% cures) under the present treatment conditions (depilation of tumor area, 10 mg/kg dihematoporphyrin ether i.p., 135 J/cm2). Considering the reduced effectiveness of photodynamic cell kill at low oxygen concentrations, the rapid induction of tumor hypoxia by PDT itself, and the high tumor cure rate, it has to be concluded that in the RIF tumor hypoxic tumor cells are inactivated by a mechanism other than direct photodynamic cytotoxicity, and are thus not limiting to PDT tumor response.