Levendag P C, Marijnissen H P, de Ru V J, Versteeg J A, van Rhoon G C, Star W M
Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):139-45. doi: 10.1016/0360-3016(88)90061-2.
Photodynamic therapy (PDT) involves the activation of photosensitizing drugs by light of appropriate wavelength. The photosensitive agent Hematoporphyrin Derivative (HPD) appears to be preferentially retained in malignant tumors; irradiation of HPD-containing tissue by light of appropriate wavelength (625 nm) and dose leads to (tumor) tissue destruction. The aim of this study is to achieve maximum tumor control probability with minimum normal tissue photosensitivity. In previous work from our laboratory it has been demonstrated that PDT has its fundamental effects on the tumor and normal tissue microcirculation. As it is well established that hyperthermia (HT) has its major effects in less well vascularized areas of the tumor, the combined modality of HT and PDT might prove to be advantageous. Moreover, suppression of sublethal damage repair by HT has been observed. To overcome the problem of poor light penetration into tissues and the high rate of recurrences following PDT with external irradiation, the combined effects of interstitial PDT with interstitial hyperthermia in a new line of animal experiments were studied in our laboratory. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of HPD, that is Photofrin II, was injected intravenously in different dose schedules (5 mg/kg, 10 mg/kg). After 24 or 48 hrs the tumors were implanted with four flexible catheters, through which either light or heat could be applied. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a dose level of 900 Joule from four linear light applicators. Heat (44 degrees C/30') was delivered by four 27 MHz radiofrequency antennas. Dose response relationships for PDT alone, HT alone and PDT combined with HT were established with cure as endpoint. This study showed that these two modalities, in the proper sequence and spacing, result in an augmented cytotoxicity on the tumor cells in vivo. With the combined modality treatment a cure rate of 41% (90 days) was obtained. As the implantation of flexible catheters is a well-known technique in radiation therapy practice, the potentiating effects of interstitial HT combined with interstitial PDT in solid tumors is very promising and clinical studies are warranted.
光动力疗法（PDT）涉及通过适当波长的光激活光敏药物。光敏剂血卟啉衍生物（HPD）似乎优先保留在恶性肿瘤中；用适当波长（625纳米）和剂量的光照射含HPD的组织会导致（肿瘤）组织破坏。本研究的目的是以最小的正常组织光敏性实现最大的肿瘤控制概率。在我们实验室之前的工作中已经证明，PDT对肿瘤和正常组织的微循环有根本性影响。由于众所周知热疗（HT）在肿瘤血管化较差的区域有主要作用，HT与PDT的联合治疗方式可能被证明是有利的。此外，还观察到HT对亚致死损伤修复的抑制作用。为了克服光穿透组织能力差以及外部照射PDT后复发率高的问题，我们实验室在一系列新的动物实验中研究了间质PDT与间质热疗的联合效果。将实验性小鼠肿瘤（横纹肌肉瘤，R - 1型）移植到WAG/Rij大鼠体内，在肿瘤平均直径达到2厘米后，以不同剂量方案（5毫克/千克、10毫克/千克）静脉注射HPD的活性成分，即光卟啉II。24或48小时后，在肿瘤中植入四根柔性导管，通过这些导管可以施加光或热。光由调谐到625纳米波长的氩染料激光系统提供，剂量率为每根光纤75 - 100毫瓦，从四个线性光 applicators照射到剂量水平为900焦耳。热量（44摄氏度/30分钟）由四个27兆赫的射频天线传递。以治愈为终点建立了单独PDT、单独HT以及PDT与HT联合治疗的剂量反应关系。这项研究表明，这两种治疗方式以适当的顺序和间隔应用，会在体内对肿瘤细胞产生增强的细胞毒性。联合治疗方式的治愈率为41%（90天）。由于在放射治疗实践中植入柔性导管是一种众所周知的技术，间质HT联合间质PDT在实体瘤中的增效作用非常有前景，值得进行临床研究。
