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大鼠R-1横纹肌肉瘤间质光动力疗法的肿瘤及正常组织反应

Tumor and normal tissue response to interstitial photodynamic therapy of the rat R-1 rhabdomyosarcoma.

作者信息

Marijnissen J P, Versteeg J A, Star W M, van Putten W L

机构信息

Department of Clinical Physics, Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

出版信息

Int J Radiat Oncol Biol Phys. 1992;22(5):963-72. doi: 10.1016/0360-3016(92)90795-j.

DOI:10.1016/0360-3016(92)90795-j
PMID:1532569
Abstract

Interstitial photodynamic therapy (IPDT) using Photofrin II (PII) as photosensitizer has been studied in the rat rhabdomyosarcoma R-1, growing on the thigh or flank of WAG-Rij rats. A light dose-response relationship has been established, for 10 mg PII/kg i.v. and irradiation 24 hr later, with local tumor control as the end point for single IPDT treatments using four cylindrical diffusors simultaneously. A light energy fluence of 150-200 Joule/cm2 (wavelength 625 nm), measured in vivo at the tumor periphery, was required for tumor control. Comparison of tumor response at 5 and 2.5 mg PII/kg with the complete dose response relationship at 10 mg PII/kg suggests drug-light dose reciprocity and indicates that in our tumor model treatment failures are not likely to be caused by variations in (tumor) tissue photosensitizer level, but rather by insufficient light dose or inadequate light dose distribution. Increasing the interval between PII administration and irradiation from 24 hr to 48 hr had no great effect on tumor response to IPDT in this study. Inspection of the original tumor site 100 days after tumor control revealed obvious loss of thigh muscle tissue. Also, recurrent tumors showed a reduced growth rate. Therefore, the relationship between tumor (re)growth and PDT-induced normal tissue damage was studied and the existence of a tumor bed effect was confirmed. The present study indicates that tumor control after a single IPDT treatment is feasible, but that PDT induced damage to a margin of the adjacent normal tissue is probably required.

摘要

使用二血卟啉醚(PII)作为光敏剂的间质光动力疗法(IPDT)已在生长于WAG-Rij大鼠大腿或胁腹的大鼠横纹肌肉瘤R-1中进行了研究。对于静脉注射10 mg PII/kg并在24小时后进行照射的情况,已建立了光剂量-反应关系,以局部肿瘤控制作为使用四个圆柱形扩散器同时进行单次IPDT治疗的终点。肿瘤控制需要在肿瘤周边进行体内测量,光能量通量为150 - 200焦耳/平方厘米(波长625纳米)。将5和2.5 mg PII/kg时的肿瘤反应与10 mg PII/kg时的完整剂量反应关系进行比较,表明药物-光剂量具有可互换性,并表明在我们的肿瘤模型中,治疗失败不太可能是由(肿瘤)组织光敏剂水平的变化引起的,而是由光剂量不足或光剂量分布不充分导致的。在本研究中,将PII给药与照射之间的间隔从24小时增加到48小时对肿瘤对IPDT的反应没有太大影响。在肿瘤得到控制100天后检查原始肿瘤部位,发现大腿肌肉组织明显缺失。此外,复发性肿瘤的生长速度有所降低。因此,研究了肿瘤(再)生长与光动力疗法诱导的正常组织损伤之间的关系,并证实了肿瘤床效应的存在。本研究表明,单次IPDT治疗后控制肿瘤是可行的,但可能需要光动力疗法对相邻正常组织的边缘造成损伤。

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