Baas P, Oppelaar H, Stavenuiter M, van Zandwijk N, Stewart F A
Division of Experimental Therapy, The Netherlands Cancer Institute.
Int J Radiat Oncol Biol Phys. 1993 Oct 20;27(3):665-70. doi: 10.1016/0360-3016(93)90394-b.
Combining the bioreductive drug SR 4233 with interstitial photodynamic therapy to improve efficacy.
RIF1 tumors were implanted subcutaneously in mice and treated with interstitial photodynamic therapy. The bioreductive drug SR 4233 (a benzotriazine which exhibits preferential cell killing under hypoxic conditions) was combined with photodynamic therapy to exploit the induced hypoxia. SR 4233 was given to mice prior to or just after illumination. The effect of multiple SR 4233 injections given over the first 3 days after treatment was also evaluated.
The results from experiments with a 24 hr interval between Photofrin and illumination showed that SR 4233 produced only a small additional growth delay compared with photodynamic therapy alone (light doses of 300 or 400 J/cm, combined with 6 x 15 mg/kg SR 4233). Some cures (6/60), however, were found in groups treated with 200 to 400 J/cm with SR 4233, whereas only two cures (2/77) occurred at light doses up to 400 J/cm after photodynamic therapy alone. Reducing the interval between Photofrin injection and illumination increased the number of cures in the combination group, although this was associated with a marked increase in toxicity. A small increase in cure rate was observed for the combination of photodynamic therapy (6 hr interval) and SR 4233, although this was not significant due to the limited number of mice that survived treatment.
Only a limited effect of combining SR 4233 and interstitial photodynamic therapy was observed in this tumor model. A possible explanation could be the rapid conversion of SR 4233 into inactive metabolites.
将生物还原药物SR 4233与间质光动力疗法相结合以提高疗效。
将RIF1肿瘤皮下植入小鼠体内，并用间质光动力疗法进行治疗。生物还原药物SR 4233（一种在缺氧条件下表现出优先细胞杀伤作用的苯并三嗪）与光动力疗法联合使用，以利用诱导的缺氧状态。在光照之前或之后给小鼠注射SR 4233。还评估了在治疗后的前3天多次注射SR 4233的效果。
Photofrin与光照间隔24小时的实验结果表明，与单独的光动力疗法相比，SR 4233仅产生了较小的额外生长延迟（光剂量为300或400 J/cm，联合6×15 mg/kg SR 4233）。然而，在用200至400 J/cm的SR 4233治疗的组中发现了一些治愈情况（6/60），而单独光动力疗法在光剂量高达400 J/cm时仅出现两例治愈情况（2/77）。缩短Photofrin注射与光照之间的间隔增加了联合治疗组的治愈数量，尽管这与毒性的显著增加有关。光动力疗法（间隔6小时）与SR 4233联合使用时观察到治愈率有小幅提高，尽管由于治疗后存活小鼠数量有限，这一提高并不显著。
在该肿瘤模型中，观察到SR 4233与间质光动力疗法联合使用的效果有限。一个可能的解释是SR 4233迅速转化为无活性代谢产物。
