van Geel I P, Oppelaar H, Oussoren Y G, van der Valk M A, Stewart F A
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam.
Int J Cancer. 1995 Jan 27;60(3):388-94. doi: 10.1002/ijc.2910600320.
The new photosensitizer, meso-tetrahydroxyphenylchlorin (mTPHC) was compared with Photofrin in the murine RIF1 tumour and in normal mouse skin. A range of mTHPC or Photofrin doses were given at intervals of 1 hr to 7 days before illumination. mTHPC-PDT resulted in much higher tumour phototoxicity with longer regrowth delays and more cures. The RIF1 tumour could be effectively treated with 30 J cm-1 (interstitial illumination) at 1 day after mTHPC, whereas 4 to 13 times higher light doses were required with Photofrin for an equivalent anti-tumour effect. High doses of mTHPC also caused more skin phototoxicity (superficial illumination) than Photofrin for the 1-day illumination interval. Evaluating both tumour and normal skin photosensitization, the largest therapeutic gain factor (TGF) for mTHPC-PDT was achieved with a low drug dose (0.15 mg kg-1) at 1 day before illumination (TGF = 5.6, relative to Photofrin PDT). The duration of cutaneous photosensitivity for mTHPC was shorter than for Photofrin. The light dose required to produce a desquamation response in 50% of the animals increased more than 20-fold over the period 1 to 7 days after high doses of mTHPC, whereas this light dose only increased by a factor of 2 from 1 to 7 days after Photofrin. The large therapeutic gains seen for mTHPC-mediated PDT compared to Photofrin, plus the rapid fading of skin photosensitization, suggest that mTHPC is a potent photosensitizer suitable for clinical testing.
将新型光敏剂中-四羟基苯基氯卟啉（mTPHC）与血卟啉衍生物（Photofrin）在小鼠RIF1肿瘤及正常小鼠皮肤中进行了比较。在光照前1小时至7天的时间间隔内给予一系列不同剂量的mTHPC或Photofrin。mTHPC介导的光动力疗法（PDT）导致更高的肿瘤光毒性，肿瘤再生延迟更长且治愈的情况更多。在给予mTHPC后1天，以30 J/cm²（间质光照）可有效治疗RIF1肿瘤，而使用Photofrin达到同等抗肿瘤效果则需要高4至13倍的光剂量。对于1天的光照间隔，高剂量的mTHPC比Photofrin引起更多的皮肤光毒性（表面光照）。综合评估肿瘤和正常皮肤的光敏化情况，在光照前1天给予低剂量药物（0.15 mg/kg）时，mTHPC-PDT获得了最大的治疗增益因子（TGF）（TGF = 5.6，相对于Photofrin PDT）。mTHPC引起的皮肤光敏持续时间比Photofrin短。高剂量mTHPC后1至7天内，使50%的动物产生脱屑反应所需的光剂量增加了20多倍，而Photofrin后1至7天该光剂量仅增加了2倍。与Photofrin相比，mTHPC介导的PDT具有显著的治疗优势，再加上皮肤光敏性迅速消退，表明mTHPC是一种适合临床测试的强效光敏剂。
