光动力治疗人胆管癌细胞荷瘤裸鼠的实验研究

目的研究光动力疗法(photodynamic therapy,PDT)对人胆管癌荷瘤裸鼠的治疗效果,探讨其抗肿瘤性、安全性及腹腔注射和瘤内注射光敏剂两种不同给药途径疗效的差异。方法人胆管癌细胞QBC939接种于Balb/c裸小鼠皮下,建立荷瘤动物模型。以血卟啉衍生物(HpD)作光敏剂,采用腹腔内和瘤内注射2种不同给药方式,后以波长630 nm的激光照射肿瘤组织,观察PDT后肿瘤体积变化和病理改变。结果接受光动力治疗的两组肿瘤生长速度明显减慢,瘤内局部注射给药组疗效与腹腔给药组差异无统计学意义(P>0.05);组织学检查见肿瘤组织有广泛坏死,各组裸鼠心、肝、肺、肾组织切片未见病理性结构改变。结论HpD,PDT对人胆管癌荷瘤裸鼠的肿瘤组织有杀伤作用,使肿瘤生长减慢;HpD-PDT杀伤胆管癌移植瘤的深度可达0.8cm;在本实验光照条件下的PDT治疗是安全的。     

光动力治疗裸小鼠胰腺移植癌的实验研究

目的 研究光动力治疗（ＰＤＴ）对胰腺癌的治疗效果,为胰腺癌寻找有效的治疗手段。方法 接种人胰腺癌细胞ＳＷ１９９０于裸小鼠皮下,建立移植癌模型,以血卟淋衍生物（ＨｐＤ）作为光敏剂,采用腹腔和瘤内局部注射两种不同方式给药,继以波长６３２．８ｎｍ的Ｈｅ－Ｎｅ激光照射肿瘤局部,观察光动力治疗后肿瘤的生长速度和组织形态学变化,并测定了肿瘤组织内脂质过氧化产物丙二醛（ＭＤＡ）的含量,对其治疗机制进行了初步探讨     

内源性光动力疗法抑制人结肠癌裸鼠种植瘤的实验研究

目的　探讨基于 5 氨基乙酰丙酸 (ALA)的光动力疗法 (PDT)对结肠癌的生长抑制作用。方法　建立人结肠癌SW 480细胞裸鼠种植瘤模型 ,经尾静脉注入ALA液 (2 5 0mg/kg体重 ) ,光敏化 3h后半导体激光仪垂直照射肿瘤 3 0min(能量密度 9J/cm2 ) ,照射后连续观察肿瘤体积 ,瘤体HE染色病理分析。结果　ALA PDT在治疗后早期产生明显的抑制肿瘤增殖作用 ,瘤体组织坏死 ,腺腔样结构解离破坏 ,延命率 40 .2 % ,体积抑瘤率达 64 .1% ,治疗后期 ,肿瘤体积仍会缓慢增长 ,但增长速度明显小于对照组。结论　SALA PDT治疗可明显抑制裸鼠结肠种植瘤生长 ,延长荷瘤裸鼠生存期 ,但仍不能完全抑制肿瘤生长。     

5-氨基乙酰丙酸代谢产物原卟啉IX在葡萄酒色斑动物模型鸡冠中的积聚

目的：研究5-氨基乙酰丙酸（5-Aminolevulini Cacid，ALA）在不同给药途径下其代谢产物原卟啉IX（protoporphyrin IX，PpIX）在葡萄酒色斑动物模型鸡冠中的聚集、分布的动态变化，探讨其治疗葡萄酒色斑的可行性。方法：以鸡冠为模型，静脉或局部真皮内注射ALA后，应用多通道光量子分析仪监测代谢产物PpIX的动态变化，组织取材切片后用共聚焦显微镜检测PpIX的分布。结果：在鸡冠组织内，ALA给药后3h PpIX出现明显聚集，分别在给药5h（静脉给药组）和4h（局部给药组）后到达高峰，静脉给药组峰值（94±15）units略高于局部给药组（73±12）units。在身体其它部位的皮肤中，PpIX聚集规律相似，但局部给药组的峰值（38±14）tinits明显低于静脉组（109±14）units。组织切片荧光检测显示PpIX弥漫性分布于真皮层中。结论：ALA的局部真皮内注射比全身给药用药量小，但能达到同样程度PpIX的积聚，有望成为葡萄酒色斑光动力学治疗的新光敏剂。     

重复光动力疗法治疗鼠C6胶质瘤

目的 观察5-氨基乙酰丙酸(5-ALA)作为光敏剂对大鼠C6胶质瘤移植瘤进行光动力疗法(PDT)的治疗作用.方法 建立大鼠胶质瘤模型,随机分成4组:A组按剂量20 mg/kg在瘤内注射5-ALA,2 h后在肿瘤局部行激光照射(单次PDT);B组操作与A组相同,但于第4、8天注射同等剂量5-ALA,重复PDT;C组给予单纯激光照射,不予任何光敏剂;D组为荷瘤对照组,不给任何治疗.治疗后测量肿瘤体积,绘制肿瘤生长曲线,以观察PDT及重复PDT对肿瘤生长的抑制情况.结果 重复光动力治疗组(B组)肿瘤体积与对照组(C、D组)比较明显缩小,比单次PDT(A组)亦较小,差异有统计学意义(P<0.05).结论 重复PDT比传统的单次PDT对大鼠C6胶质瘤移植瘤肿瘤的抑制效果更加明显.     

光动力疗法治疗恶性肿瘤作用机制的研究进展

【摘要】 光动力疗法(PDT)是继手术、放化疗等传统治疗肿瘤手段外的一种新的抗肿瘤模式。PDT机制目前尚不完全清楚, 已知其利用肿瘤细胞高摄取光敏剂的特性, 使用相应波长的激光照射, 使光敏剂产生单线态氧或其他活性氧, 通过非细胞凋亡途径或直接高效诱导凋亡或导致肿瘤组织坏死杀死癌细胞。PDT也可损伤肿瘤组织的血管内皮细胞及介导自身免疫系统的激活。     

局部光动力疗法在损容性皮肤病应用中的进展

光动力反应是在光敏剂和光辐射作用下所导致的依赖于氧化反应的一种组织反应。光动力疗法最初是作为治疗各种人类肿瘤的经验方法，现在该疗法不仅应用于非黑素细胞瘤，而且还用于痤疮、光线性角化病、基底细胞癌等损容性皮肤病的治疗。近十年来，光动力疗法在全世界得到了普及，其治疗需要光敏剂、光源照射及病变组织中的氧这三个条件同时存在。由于系统应用光敏剂使光毒性延长，故光敏剂药物在皮肤科倾向于局部使用。本文就光敏剂、光源及其临床疗效作如下综述。     

5-氨基乙酰丙酸介导的光动力学治疗人脑胶质瘤

颅内胶质瘤是临床上常见病、多发病。目前多采用手术、放疗、化疗等综合治疗，但治疗效果仍不甚满意。目前在临床上广泛使用的血卟啉制剂所介导的肿瘤光动力治疗(photodynamic therapy，PDT)虽然在肿瘤的临床诊断和治疗中都取得了肯定的疗效，但仍有很多不足之处。5-氨基乙酰丙酸(5-aminolevulinicacid，5-ALA)是目前光动力疗法领域中最活跃的光敏剂前体物，     

皮肤病光动力疗法系列讲座（七）——δ-盐酸氨基戊酸光动力疗法在皮肤癌前病变及皮肤癌中的应用

光动力疗法（photodynamic therapy,PDT）是通过光敏剂进入体内受适当波长的激光产生一系列化学毒性效应,产生中活性物质,与相应靶组织结合,导致不可逆的组织损伤和细胞死亡的一种治疗方法。自1990年加拿大学者Kennedy等报道成功治疗皮肤癌以来,δ-盐酸氨基戊酸（5-aminolevulinic acid,ALA）光动力疗法现已成为研究和应用的热点。现将δ-盐酸氨基戊酸光动力疗法（ALA—PDT）治疗皮肤癌及癌前病变的可能作用机制、激光照射方法、临床应用及不良反应介绍如下。     

大鼠膀胱癌模型的光动力学治疗

目的　验证采用新型光敏剂的光动力学治疗方法对于SD大鼠膀胱癌动物模型的有效性。方法　使用 0 .0 5 %N 丁基 N(4 羟丁基 )亚硝胺 (BBN)诱导成功的SD大鼠随机分为试验组2 0只和对照组 7只。实验组大鼠用剂量为 50mg/kg体重光敏剂溶液灌胃 ,2 4h后打开膀胱进行激光照射 ,能量为 50J/cm2 ,72h后取肿瘤标本送病理分析和DNA含量测定 ,对照组术前不灌药物。结果　光动力学治疗法 (PDT)治疗后试验组的肿瘤坏死发生率和面积均高于对照组 ,差异有显著性 (P <0 .0 5)。样本的平均DNA质量均数 :实验组 9.50 5pg,对照组 1 4 .2 69pg,差异有显著性 (P<0 .0 5)。结论　以CDHS80 1作为光敏剂的光动力学治疗对于SD大鼠膀胱癌模型是有效的     

In vitro and in vivo photosensitizing capabilities of 5-ALA versus photofrin in vascular endothelial cells

BACKGROUND AND OBJECTIVE: The objective of the present study was to evaluate the feasibility of photodynamic therapy (PDT) for complicated hemangiomas. The photosensitizing activities of 5-aminolevulinic acid (5-ALA) and Photofrin were evaluated in vitro with human dermal microvascular endothelial cells (MEC) and in vivo with the chicken cox comb. STUDY DESIGN/MATERIALS AND METHODS: The in vitro absorption and photosensitizing activities of 5-ALA and Photofrin were examined in a MEC culture system. The percentages of MEC killed by different drug concentrations at a wavelength of 630 nm were measured by either live/dead or lactate dehydrogenase-released assays. Similarly, the in vivo biological activities of 5-ALA and Photofrin exposed to different total light dosages at 630 nm were studied by determining the amount of necrosis produced in chicken combs. RESULTS: MEC incubated with 5-ALA at a concentration of 35 microg/ml and exposed to laser light at 630 nm at a power density of 100 mW/cm2 showed a 50% cell kill. MEC incubated with Photofrin at a concentration of 3.5 microg/ml and exposed to laser light at 630 nm at a power density of 100 mW/cm2 showed a 50% cell kill. Chicken combs that received 200 mg/kg of 5-ALA exposed to laser light at 630 nm at a power density of 100 mW/cm2 had an injury depth of 362.5+/-27.6 microm at histologic examination. Combs exposed to a power density of 100 or 120 mW/cm2 showed injury depths of 732.5+/-29.1 and 792.5+/-36.0 microm, respectively. Chicken combs that received 2.5 mg/kg of Photofrin exposed to laser light at 630 nm at a power density of 80 mW/cm2 had an injury depth of 535.6+/-22.3 microm at histologic examination. Combs exposed to a power density of 100 or 120 mW/cm2 showed injury depths of 795.8+/-32.5 and 805.2+/-49.1 microm, respectively. CONCLUSION: Both 5-ALA and Photofrin have the capability to destroy MEC in vitro and vasculature in vivo. However, Photofrin achieved a higher degree of cell kill and tissue destruction at lower drug concentrations and at lower power densities.     

5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

目的观察5-氨基乙酰丙酸（5-ALA）介导的光动力学治疗对裸鼠人胃癌移植瘤的治疗作用。探索5-ALA介导的光动力学（PDT）治疗胃癌的可能机制。方法以MGC-803人胃癌细胞制备裸鼠人胃癌移植瘤模型：整体荧光成像系统下观察动物瘤体发出的荧光信号：测量荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天的裸鼠肿瘤大小并计算肿瘤体积：末次测量后切除肿瘤行病理检查和透射电镜观察，TUNEL法检测组织细胞凋亡。结果常规方法培养MGC一803人胃癌细胞并接种裸鼠．可以成功制备出裸鼠人胃癌移植瘤的模型：荷瘤裸鼠肿瘤组织在特定波长的荧光激发下可发出特有的红色荧光。荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天4组间的肿瘤体积差异有统计学意义（肚1003．086，P=0．000），PDT治疗组明显小于其他3组；病理检查提示．PDT治疗后肿瘤细胞大片凝固性坏死；透射电镜观察提示，PDT治疗组肿瘤组织存在大量死亡细胞及部分凋亡细胞：TUNEL法检测发现，PDT治疗组的肿瘤组织凋亡指数显著高于其他3组（χ^2=18．237．P=0．000）。结论5-ALA介导的PDT对于裸鼠人胃癌移植瘤具有明显的治疗效果．而单纯给予5-ALA或激光辐射对肿瘤无明显抑制作用；肿瘤细胞的坏死及凋亡是5-ALA介导的PDT产生细胞毒作用的重要机制。     

Photoeradication of Helicobacter pylori using 5-aminolevulinic acid: preliminary human studies

BACKGROUND AND OBJECTIVES: Helicobacter pylori (HP) is an endemic pathogenic bacterium causing gastritis and gastroduodenal ulceration in humans and is linked to the development of gastric malignancies. These first human in vivo studies investigated the photoeradication of HP using laser and white light. STUDY DESIGN/MATERIALS AND METHODS: In 13 HP-positive volunteers, a zone of gastric antrum was irradiated with laser (410 nm, 50 J/cm(2)) or endoscopic white light (10 J/cm(2)) 45 minutes after oral 5-aminolevulinic acid (5-ALA) 20 mg/kg. HP-eradication was assessed by biopsy urease test and HP-culture from irradiated and control zones 5 minutes, 4 and 48 hours post-irradiation. RESULTS: A maximum eradication effect was achieved at 4 hours post-irradiation when 85% of biopsies in the monochromatic and 66% in the white light exposed zones, and 58 and 33% in the respective control zones were HP-negative. CONCLUSIONS: HP numbers were greatly reduced following exposure to 5-ALA and either laser or white light in vivo. Photoeradication appears feasible, but further light dosimetry and the development of convenient application methods is required.     

Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid

OBJECT: Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain. METHODS: Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight). Tumors were induced by cortical inoculation of C6 cells and 9 days later, magnetic resonance (MR) images were obtained. On Day 10, animals were given 5-ALA (100 mg/kg body weight) and their brains were irradiated (100 J/cm2) 3 or 6 hours later. Seventy-two hours after irradiation, the brains were removed for histological examination. Irradiation of brains after administration of 5-ALA resulted in superficial cortical damage, the effects of which were not different from those of the irradiation alone. Induction of cold injury in combination with 5-ALA and irradiation slightly increased the depth of damage. In the group that received irradiation after intravenous administration of Photofrin II the depth of damage inflicted was significantly greater. The extent of damage in response to 5-ALA and irradiation in brains harboring C6 tumors corresponded to the extent of tumor determined from pretreatment MR images. CONCLUSIONS: Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.     

5-氨基乙酰丙酸光动力学疗法对两种人卵巢癌细胞的体外杀伤作用

目的：探讨5-氨基乙酰丙酸（5-ALA）光动力学疗法（photodynamic therapy,PDT）对体外培养人卵巢癌SKOV3和AO细胞的杀伤作用。方法：于体外培养的SKOV3和AO细胞分别加入不同浓度的5-ALA（0．1、0．5、1．0、2．5、12．5mmol／L）孵育4h,以波长为630nm的半导体激光进行照射,照射能量密度分别为0．1、0．5、2．5、12．5J／cm^2。用四唑盐（MTT）比色法测定细胞存活率,并与单纯药物对照组（不同浓度5ALA孵育、无光照）、单纯光照组（无5-ALA孵育、不同能量密度光照）与阴性对照组（无药物孵育、无光照）进行比较。计算5ALA—PDT对SKOV3和AO细胞的半数杀伤浓度（IC50）。结果：5-ALA—PDT处理后两种卵巢癌细胞存活率均明显下降（P〈0．05）,提示5ALA—PDT对体外培养的人卵巢癌SKOV3和AO细胞均有杀伤作用,其杀伤作用随5-ALA的浓度和激光能量密度增加而增加,当5-ALA浓度超过2．5mmol／L或照射能量密度超过2．5J／cm^2时细胞存活率变化不明显。单纯药物对照组、单纯光照组的细胞存活率与阴性对照组相比差异无显著性（P〉0．05）。5-ALA-PDT对两种卵巢癌细胞杀伤效应强弱不同,对SKOV3及AO细胞的半抑制浓度（IC50）分别为0．34mmol／L和2．50mmol／L,两者差异有显著性（P〈0．05）。结论：5-ALA-PDT可有效杀伤体外培养的人卵巢癌细胞SKOV3和AO细胞,且对两种细胞的杀伤作用有差异,对SKOV3细胞株的杀伤效应要强于AO细胞株。     

Intraoperative photodynamic diagnosis for spinal ependymoma using 5-aminolevulinic acid: technical note

OBJECTIVE: The fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is a well established method for the treatment of brain tumor, especially malignant glioma. However, there is no report on photodynamic diagnosis (PDD) for spinal tumor. In the present study, we evaluated the usefulness of PDD for spinal ependymoma using 5-ALA. METHODS: Three patients with spinal ependymoma received oral doses of 5-ALA (20 mg/kg body weight) 2 hours before anesthesia induction. Intraoperatively, fluorescence was observed with a 420 nm sharp cut filter after excitation with a violet semiconductor laser (405 nm) and was verified by analysis of fluorescent spectra. Residual fluorescent samples taken from the tumor cavity were examined histologically RESULTS: Fluorescence peaked at 636nm in the removed tumors in all cases. Fluorescent tissue tended to exist at the cranial and caudal portion in the tumor cavity or around the anterior median fissure. The residual fluorescent tissue was not detected after removal of the tumor in case 1. The residual fluorescent tissue was composed of tumor cells and ependymal lining in case 2 or the infiltrated inflammatory cells and vascular endothelial cells in case 3. Postoperative magnetic resonance (MR) imaging showed no residual tumor in any of the cases. CONCLUSION: The results of this study indicate the usefulness of 5-ALA-induced tumor fluorescence in guiding resection of spinal ependymoma. 5-ALA-induced porphyrin fluorescence may label spinal ependymomas easily and clearly enough to enhance the completeness of tumor removal.     

Photodynamic therapy for human malignant mesothelioma in the nude mouse

Photodynamic therapy (PDT) utilizes a photoactivatable preparation, Photofrin II, which selectively localizes in cancerous tissue and produces substances toxic to that tissue when activated by light. Whether PDT would be able to selectively destroy human malignant mesothelioma was investigated by using a human-derived malignant mesothelioma tumor subcutaneously implanted in nude mice. Human malignant mesothelioma was grown subcutaneously to a size of 0.2-0.4 cm3. Selective retention of Photofrin II was studied by measuring light-induced inhibition of cytochrome c oxidase activity in tumor, heart, and lung. Photofrin II was retained in greater quantities in tumor than in heart or lung at 24 hr after injection. Using laser light at 630 nm under varying conditions, tumor growth was measured every 2 days following PDT for 18 days. All PDT regimens were successful in destroying malignant mesothelioma. Photofrin II at 5 mg/kg was superior to 2 mg/kg (P less than 0.005), light delivered at 50 mW/cm2 x 2 hr was superior to that delivered at 200 mW/cm2 x 30 min (P less than 0.05), and a total fluence of 180 J/cm2 was equivalent to 360 J/cm2 in affecting tumor growth. Ten of 12 mice treated at 50 mW/cm2 became tumor-free and remained so for 30 days following treatment. We concluded that PDT was effective against human malignant mesothelioma in a nude mouse model without adversely affecting the animal. A role for PDT in treating patients with malignant mesothelioma may exist.     

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.     

Photodynamic activity of lutetium-texaphyrin in a mouse tumor system.

BACKGROUND AND OBJECTIVE: New photosensitizers proposed for photodynamic therapy (PDT) treatment of tumors need to be evaluated in animal models to determine the parameters needed for treatment. They also need to be compared with existing photosensitizers for efficacy. We examined the PDT response to lutetium-texaphyrin (PCI-0123) in a mouse mammary adenocarcinoma model and compared it with the PDT response seen when using Photofrin. STUDY DESIGN/MATERIALS AND METHODS: DBA/2 mice with SMT-F tumors were used to explore PCI-0123 toxicity, laser light dose, and drug dose effects on PDT response and to determine the most effective time for light application. The PDT response of PCI-0123-treated tumors was compared with that of Photofrin-treated tumors. RESULTS: Treatment of tumors with 150 J/cm2 of 740 nm laser light 5-6 hr after PCI-0123 administration (40 mg/kg) resulted in a 100% response rate and a 55% cure rate. Tumors treated with 150 J/cm2 of 630 nm laser light 24 hr after Photofrin administration (10 mg/kg) resulted in a 67% response rate and a 16% cure rate. CONCLUSION: PCI-0123 was found to be a more effective photosensitizer than Photofrin.     

2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) in a nude rat glioma model: implications for photodynamic therapy

BACKGROUND AND OBJECTIVE: In this study, we evaluated 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor) as a photosensitizer for the treatment of malignant gliomas by photodynamic therapy (PDT). STUDY DESIGN/MATERIALS AND METHODS: We performed in vivo reflection spectroscopy in athymic rats to measure the attenuation of light in normal brain tissue. We also studied HPPH pharmacokinetics and PDT effects in nude rats with brain tumors derived from stereotactically implanted U87 human glioma cells. Rats implanted with tumors were sacrificed at designated time points to determine the pharmacokinetics of HPPH in serum, tumor, normal brain, and brain adjacent to tumor (BAT). HPPH concentrations in normal brain, BAT and tumor were determined using fluorescence spectroscopy. Twenty-four hours after intravenous injection of HPPH, we administered interstitial PDT treatment at a wavelength of 665 nm. Light was given in doses of 3.5, 7.5 or 15 J/cm at the tumor site and at a rate of 50 mW/cm. RESULTS: In vivo spectroscopy of normal brain tissue showed that the attenuation depth of 665 nm light is approximately 30% greater than that of 630 nm light used to activate Photofrin, which is currently being evaluated for PDT as an adjuvant to surgery for malignant gliomas. The t1/2 of disappearance of drug from serum and tumor was 25 and 30 hours, respectively. CONCLUSION: Twenty-four hours after injection of 0.5 mg/kg HPPH, tumor-to-brain drug ratios ranged from 5:1 to 15:1. Enhanced survival was observed in each of the HPPH/PDT-treated animal groups. These data suggest that HPPH may be a useful adjuvant for the treatment of malignant gliomas.