Furukawa K, Yamamoto H, Crean D H, Kato H, Mang T S
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York 14263 USA.
Lasers Surg Med. 1996;18(2):157-66. doi: 10.1002/(SICI)1096-9101(1996)18:2<157::AID-LSM5>3.0.CO;2-R.
Photofrin is the photosensitizer currently used in most clinical trials examining the efficacy of photodynamic therapy (PDT) for the treatment and/or palliation of neoplasia. Although this drug has been shown to be efficacious in many of these trials, it possesses less than ideal qualities for use in a systemically administered photosensitizer. A new photosensitizer, 2-[l-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was developed for PDT. HPPH possesses more rapid clearance from skin and greater cytotoxicity per drug dose than Photofrin. The aims of this study were to: (1) examine the uptake and retention of HPPH in tissues undergoing malignant transformation using laser-induced fluorescence, and (2) evaluate the efficacy of HPPH and 665 nm light in treating carcinogen-induced tumors of the hamster buccal cheek pouch.
STUDY DESIGN/MATERIALS AND METHODS: The model of tissue transformation was the carcinogen (9,10-dimethyl-1, 2-benzanthracene)-induced premalignant and malignant lesions of the hamster buccal cheek pouch. Following induction of the specific transformation stages, hamsters were injected intraperitoneally with 0.5 mg/kg HPPH. Subsequently, the buccal mucosa was examined for fluorescence at various times up to 72 hours after photosensitizer injection.
Uptake studies of HPPH showed highest fluorescence levels in tissues 48 hours after HPPH injection. Fluorescence levels of tissues increased significantly as follows. Normal < dysplasia < papillomas < squamous cell carcinomas. Carcinogen-induced tumors in 14 hamsters were treated with surface illuminations of red light (665 nm) via fiber optics coupled to an argon-ion pumped dye laser 48 hours after intraperitoneal injection with either 0.5 or 1.0 mg/kg HPPH. Complete necrosis of tumor tissues 7 days following PDT was observed in 57% (4/7) with 0.5 mg/kg and 86% (6/7) with 1.0 mg/kg HPPH.
光敏剂卟吩姆钠是目前大多数用于检查光动力疗法（PDT）治疗和/或缓解肿瘤疗效的临床试验中所使用的光敏剂。尽管该药物在许多此类试验中已显示出疗效，但作为一种全身给药的光敏剂，它具有一些不尽如人意的特性。一种新型光敏剂，2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a（HPPH），被研发用于光动力疗法。与卟吩姆钠相比，HPPH从皮肤清除的速度更快，且每单位药物剂量的细胞毒性更大。本研究的目的是：（1）使用激光诱导荧光检查HPPH在发生恶性转化的组织中的摄取和滞留情况，以及（2）评估HPPH和665nm光治疗致癌物诱导的仓鼠颊囊肿瘤的疗效。
研究设计/材料与方法：组织转化模型为致癌物（9,10-二甲基-1,2-苯并蒽）诱导的仓鼠颊囊癌前病变和恶性病变。在诱导出特定的转化阶段后，给仓鼠腹腔注射0.5mg/kg的HPPH。随后，在注射光敏剂后的72小时内，在不同时间检查颊黏膜的荧光情况。
HPPH的摄取研究显示，在注射HPPH后48小时，组织中的荧光水平最高。组织的荧光水平按以下顺序显著升高：正常组织＜发育异常组织＜乳头状瘤＜鳞状细胞癌。在腹腔注射0.5或1.0mg/kg HPPH 48小时后，通过与氩离子泵浦染料激光耦合的光纤对14只仓鼠的致癌物诱导肿瘤进行红光（665nm）表面照射治疗。光动力疗法7天后，观察到0.5mg/kg HPPH组有57%（4/7）的肿瘤组织完全坏死，1.0mg/kg HPPH组有86%（6/7）的肿瘤组织完全坏死。
