Enhanced tumor control following sequential treatments of photodynamic therapy (PDT) and localized microwave hyperthermia in vivo

Photodynamic therapy (PDT), or photoradiation therapy (PRT), utilizing hematoporphyrin derivative (HPD) as photosensitizer and an argon-dye laser system as the light source, was used alone and in combination with localized microwave hyperthermia (2450 MHz) to treat axillary tumors of the SMT-F mammary carcinoma in mice. Thirty-minute heat treatments were applied either immediately before or immediately after a standard PDT treatment of 630 nm light at 75 mW/cm2 for 30 min (135 J/cm2) given 24 hr post-7.5 mg/kg HPD, intraperitoneally (i.p.). Tumor control as judged by lack of tumor regrowth 35 days or longer after the combined treatments was compared to that following each treatment when given alone. Little or no enhancement of tumor control was seen when sublethal temperatures of 37.5, 38.5, and 39.5 degrees C were applied for 30 min immediately following the PDT treatment. However, increasing levels of enhancement were seen when heat treatments of 40.5 and 41.5 degrees C or 44.5 degrees C, given for 30 min, were applied immediately before or after the photodynamic treatment.     

Photodynamic therapy of C3H tumours in mice: Effect of drug/light dose fractionation and misonidazole

C3H mammary carcinomas transplanted to the feet of mice were treated with haematoporphyrin derivative (HPD) or Photofrin II(PII) and laser light at 630 nm. While fluence rates lower than 100 mW cm⁻² gave minimal hyperthermic effects, a slight but significant growth delay was observed in unsensitized tumours exposed to a fluence rate of 150 mW cm⁻² which induced tumour temperatures in the range 40–50°C. Different modes of fractionation of the light fluence and of the HPD dose were tested but were found to give poorer rather than better results than the application of a single light exposure 24 h after intraperitoneal injection of HPD. Different PII doses were applied together with different light fluences, keeping the product of the drug dose and light fluence constant. In the dose range 6.25–50 mg/kg body weight the resulting effect on tumours was constant, allowing for a slight effect of hyperthermia at the highest light fluences, and possibly a photodegradation of PII. Misonidazole given before photodynamic treatment (PDT) slightly reduced the effect of PDT on the tumour growth. When given after PDT, however, misonidazole improved the therapeutic results significantly.     

Photodynamic therapy of superficial bladder tumors

Photodynamic therapy (PDT), using hematoporphyrin derivative (HPD) and the red light (wavelength 630 nm) of an argon-dye laser as the source of excitation energy was performed on 46 patients with superficial bladder tumors. Two methods of laser irradiation, (1) focal PDT using a 400 micron quartz fiber through a cystourethroscope in 22 patients with superficial bladder tumors and (2) whole bladder wall total PDT using a motor-driven laser light scattering device in 24 patients with multifocal carcinoma in situ and/or dysplasia of bladder mucosa associated with multicentric concurrent superficial tumors, were used. The patients in (2) had been referred for total cystectomy, and 19 of these 24 patients had a history of several transurethral resections, hyperthermia and/or instillation therapy. HPD 2-4 mg/kg was i.v. injected 48 to 72 hours before PDT. Judging from the results of 60 protrusions treated by focal PDT, the light power should be 200 mW/cm2 for 5-10 minutes or more and the total light energy should be 100 J/cm2 or more in tumors up to 2 cm in size. With focal PDT, 4 of the 22 patients had no recurrence with the mean tumor free time of 20.8 months. In 6 of the 24 patients treated with total PDT using 10, 20 or 30 J/cm2 of light energy, there was no recurrence with a mean tumor-free time of 7.5 months and there was no significant relationship between the recurrence rate and total light energy used.     

Synergistic enhancement of the efficacy of the bioreductively activated alkylating agent RSU-1164 in the treatment of prostatic cancer by photodynamic therapy

Bioreductively activated alkylating agents (BAA) require metabolic reduction to become cytotoxic. Hypoxia induces a massive increase in reductive metabolism activating BAA to their cytotoxic form. One of these BAA agents is cis-2,3-dimethyl 1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol referred to as RSU-1164. In a hypoxic environment, RSU-1164 is activated to a highly reactive bifunctional alkylating agent capable of crosslinking macromolecules which results in cell death. Photodynamic therapy (PDT) is a treatment modality which consists of the initial accumulation of hematoporphyrin derivative (HPD) within a tumor followed by the activation of the HPD by 630 nm. light to induce a cytotoxic response. The precise mechanism of PDT is not known, however, two actions of the activated HPD have been documented. The first is a direct cytotoxic effect, secondary to singlet oxygen production. The second is through vascular collapse and subsequent hypoxia. The combination of a chemotherapeutic agent like RSU-1164, which is activated by hypoxia, with PDT to produce such hypoxia, therefore, should greatly increase the efficiency and utility of RSU-1164. To test this hypothesis, Copenhagen rats bearing established Dunning R-3327 AT-2 prostate cancers were treated with PDT treatment alone (HPD 20 mg./kg. injected IP and then 24 hr. later, the tumor exposed to 630 nm. light at 400 mW/cm.2 for 30 min. [total dose 720 J/cm.2]), RSU-1164 alone (injected IP at a dose of 200 mg./kg.) or with the combination of this PDT treatment plus RSU-1164 given 30 min. before light exposure. These results demonstrated that this combinational treatment synergistically produces a greater retardation in the growth of the AT-2 tumor than either of the monotherapies of RSU-1164 or PDT alone.     

Photodynamic therapy using Verteporfin (benzoporphyrin derivative monoacid ring A, BPD-MA) and 630 nm laser light in canine esophagus

BACKGROUND AND OBJECTIVE: Verteporfin is a new photosensitizer with short-term skin photosensitivity. The objective of this preclinical study was to find the light dose that effectively ablates canine esophageal mucosa when delivered 30 minutes after Verteporfin injection. STUDY DESIGN/MATERIALS AND METHODS: Verteporfin was administered intravenously (0.75 mg/kg). 630 nm light from KTP/Dye laser was delivered using an esophageal Photodynamic therapy (PDT) balloon. In Phase I study, animals were treated 30 minutes after drug injection using 40, 60, and 80 J/cm to find the desired light dose. Using results from phase I and application of reciprocity principle (light dose vs. plasma concentration of drug), additional light doses were calculated for delivery at other times. In phase II, animals were treated at 15, 60, and 120 minutes, using the calculated light doses of 60, 145, and 200 J/cm, respectively. Animals were followed for 2 days to 4 weeks. RESULTS: In Phase I, 80 J/cm at 30 minutes induced total mucosal ablation. In Phase II, light doses of 60, 145, and 200 J/cm induced similar mucosal injuries when delivered at 15, 60, and 120 minutes, respectively. CONCLUSIONS: Effective mucosal ablation in canine esophagus was achieved using Verteporfin and 630 nm light doses of 60, 80, 145, and 200 J/cm when delivered at 15, 30, 60, and 120 minutes after the drug injection, respectively.     

Photodynamic therapy of human ocular cancer

Photodynamic therapy (PDT), also known as photoradiation therapy, was employed in five patients with ocular tumors that had been photosensitized to hematoporphyrin derivative (HPD). In each case more conventional treatment had failed to control the tumor, or the patient was considered a poor candidate for surgical intervention because of advanced age or general health. Intravenous administration of 2.5-3.0 mg/kg HPD was followed by PDT 2-4 days later, using a dye laser tuned to a wavelength of 632 nm. Laser light was delivered either by a fiber optic probe maintained at a fixed distance, or via a slit lamp system, for intervals of up to 20 minutes. The levels of energy applied were mainly below 420 Joules/cm2, but for tumors less than 1 mm diameter energy levels were as high as 3000 J/cm2 with a conservative power value as low as 20 mW/cm2. Tumor response to PDT was disappointing. Although substantial superficial tumor necrosis occurred in several cases, it did not extend to the deeper levels of tumor tissue. In each instance surgical intervention became necessary. Deficiencies in the procedure are discussed.     

Photodynamic effects of SIM01, a new sensitizer, on experimental brain tumors in rats

BACKGROUND: Glioblastomas are the third most common cause of cancer death in patients between 15 and 35 years old. Literature suggests that PDT could represent a promising treatment, providing that sensitizers could accumulate within the cancer tissues despite the blood-brain barrier. METHODS: Distribution and PDT effect of SIM01, a promising photosensitizer, have been evaluated on orthotopic C6 tumor model in rats by comparison with HPD and m-THPC. Pharmacokinetics had been analyzed with fluorescence and ROS. Photodynamic treatment was done using a 630-nm light with an energy density of 100 J cm(-2) for HPD and a 652-nm light with an energy density of 20 J cm(-2) for m-THPC and SIM01. RESULTS: The correlation between fluorescence and ROS dosimetry was found to be excellent. An optimal concentration was found after 12 hours for SIM01 (4 mg/kg), 24 hours for HPD (10 mg/kg), and 48 hours for m-THPC (4 mg/kg). The best normal tissue/cancer ratio of concentration had been found after 12 hours for SIM01 and 48 hours for HPD and m-THPC. Pathological examinations after PDT showed that the criteria for histology of glioblastic origin were absent in SIM01-treated rats 12 hours after injection but were present in 50% of rats treated 24 hours after injection and in all after a 48-hour delay. Mean survival of rats treated 12 or 24 hours after SIM01 injection was significantly improved compared with controls, HPD-, or m-THPC-treated groups. Survival of rats treated 12 or 24 hours after SIM01 injection reached 20 days but decreased for longer delays. On the contrary, survival reached 18 days at the maximum for rats treated 48 hours after m-THPC or HPD injection. CONCLUSIONS: Our results confirm that PDT is a promising treatment for glioblastomas. SIM01 efficacy is as efficient as m-THPC but with much more favorable pharmacokinetics.     

Effect of hematoporphyrin derivative photoradiation therapy on survival in the rat 9L gliosarcoma brain-tumor model

Intracerebral tumors were produced in 99 rats by stereotaxic implantation of 9L gliosarcoma brain-tumor cells. Hematoporphyrin derivative (HPD), 10 or 20 mg/kg, was administered as an intravenous bolus 24 or 48 hours before irradiation of the tumor region with light from an argon pumped-dye laser (632 nm). Laser light, at a dose of 30, 60, or 200 joules/sq cm, was delivered through a craniectomy 10 or 13 days after tumor implantation. Survival times were significantly prolonged in rats exposed to laser light at a dose of 200 joules/sq cm 24 hours after administration of HPD, 20 mg/kg.     

Photodynamic therapy: Optimal treatment parameters in murine fibrosarcoma

We have investigated the efficacy of photodynamic therapy (PDT) by using two preparations of haematoporphyrin derivative (HPD) that demonstrated different biological activities against experimental murine fibrosarcoma RIF-1 in C3H/He mice. We have been able to demonstrate a minimum clonogenic survival rate of 0.25% by using the more active HPD at 20 mg/kg with a 40-h retention time and a total laser light dose of 100 J/cm². Further, we noted that clonogenic survival rates of 21.6% and 25.0% respectively could be achieved by using the less active HPD (at 20 mg/kg) with a laser light dose of 150 J/cm², or the more active HPD (at 20 mg/kg) with a laser light dose of 20 J/cm². In both cases necrosis of the surrounding normal tissue was absent. Necrosis of the normal tissue surrounding the tumour was shown to be associated with high laser energy (100 J/cm² and higher) in conjunction with a high dose (20 mg/kg) of the more active HPD. A comparison of survival curves as a function of laser energy for the RIF-1 cells following PDT with the two different preparations of HPD showed a difference in the kinetics of cell death. A curve with a shoulder region and aD _o (mean lethal dose) of 41 J/cm² was obtained when the less active HPD was used, whereas PDT using the more active HPD resulted in a curve with no shoulder and aD _o of 16 J/cm².     

Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model

OBJECT: Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of resection, indicating that a more aggressive local therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment involving the administration of a tumor-localizing photosensitizing drug, in this case aminolevulinic acid (ALA). The effect depends on the total light energy delivered to the target tissue, but may also be influenced by the rate of light delivery. METHODS: In vitro experiments showed that the sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended on the rate of light delivery (fluence rate). The BT4C tumors were established intracranially in BD-IX rats. Microfluorometry of frozen tissue sections showed that photosensitization is produced with better than 200:1 tumor/normal tissue selectivity after ALA injection. Four hours after intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was delivered interstitially over 15 (high fluence rate) or 90 (low fluence rate) minutes. Histological examination of animals treated 14 days after tumor induction demonstrated extensive tumor necrosis after low-fluence-rate PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil infiltration in tumor tissue was increased by PDT, but was similar for both treatment regimens. Low-fluence-rate PDT administered 9 days after tumor induction resulted in statistically significant prolongation of survival for treated rats compared with nontreated control animals. CONCLUSIONS: Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the survival for tumor-bearing animals.     

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.     

Interstitial laser photochemotherapy of rhodamine-123-sensitized rat glioma

The effect of interstitial laser photochemotherapy with the mitochondrial-specific intravital dye rhodamine-123 (Rh-123) was studied using a malignant rat glioma model system (RT2). Tumors were transplanted subcutaneously into the flank of athymic mice and into the cerebrum of adult rats. The Rh-123 photosensitization was produced by direct intratumoral injection of Rh-123 into the mouse RT2 flank tumors and by intravenous Rh-123 administration to adult rats with implanted RT2 intracerebral tumors. Intratumoral irradiation with 150 mW of argon laser light for an exposure time of 15 minutes was performed using a conical sapphire-tipped quartz optical fiber. Control groups of animals received either no treatment, Rh-123 injections, or administration of 150 mW of argon laser light for 15 minutes. Both flank and intracerebral tumors showed progressive diminution in size after treatment with Rh-123 photochemotherapy. There was no evidence of tumor recurrence in 60% of Rh-123 photochemotherapy-treated tumors. Recurrences in tumors treated with Rh-123 photochemotherapy usually appeared at the periphery of the original tumor at 10 days after treatment. Histologically, photochemotherapy-treated intracerebral tumors showed progressive shrinkage with increasing tumor necrosis over time. The finding of residual or recurrent tumor at the periphery of the original tumor mass suggests that the lack of penetration of the blue-green (argon) light was responsible for preventing complete tumor ablation. Our results suggest that Rh-123 photochemotherapy can destroy malignant gliomas in vivo; however, the poor penetrability of the photoactivating blue-green light may limit the effectiveness of this treatment for large or extensively invasive tumors.     

PSD-007介导的光动力疗法治疗小鼠骨肉瘤的实验研究

目的 观察光敏剂PSD-007对小鼠骨肉瘤细胞LM-8的体外及体内光动力效应.方法 PSD-007与LM-8细胞共同孵育后以激光照射,应用MTT法测定光密度(OD540)值,计算抑制率.40只C3H小鼠接种LM-8细胞,皮下瘤块直径7～8 mm时随机分为:(1)对照组,空白对照、生理盐水加光照、注射PSD-007不光照;(2)光动力治疗组,分别注射5mg/kg、10mg/kg PSD-007,6 h后以激光照射.1周后测量瘤体大小、重量,计算抑瘤率并行病理学检查.C3H小鼠30只建立肿瘤模型,肿瘤直径达10～12mm时,分别行肿瘤边缘切除无光动力治疗(对照组)、边缘切除后240 J/cm2光动力治疗及边缘切除后360 J/cm2光动力治疗.4周后比较肿瘤复发率.结果 体外只光照或只注射PSD-007对LM-8细胞均无杀伤作应.PSD-007浓度越高、激光照射强度越大,LM-8细胞OD540值越小.PSD-007浓度>4μg/ml,光照强度>6 J/cm2时,抑制率>50%.光镜下细胞形态呈坏死或凋亡样改变.体内实验显示光动力治疗组的肿瘤体积及瘤重均减小,肿瘤边缘切除高强度激光照射组的复发率较对照组低.结论 PSD-007对LM-8细胞有明确的光动力抑制效应,其作用大小取决于其浓度和激光照射强度.光动力疗法可以降低肿瘤边缘切除后的复发率.

Abstract：

Objective To evaluate the PSD-007-mediated photodynamic effect on mouse osteosarcoma cell line LM-8, both in vitro and in vivo. Methods LM-8 cells were incubated with different concentrations of PSD-007 for 4 hours and then followed different laser irradiations. After photodynamic therapy (PDT), cell viability was measured using MTT assay and the optical density in each experiment was measured at 450 nm with a micro plate reader. The inhibition rate of cell growth was calculated. Four-week-old female C3H mice were used for implantation of LM-8 cells. When the diameter of tumor reached up to 7-8 mm, the mice were randomly divided into following groups: 1) control group, including untreated control, saline with laser irradiation, PSD-007 without laser irradiation; 2) PDT group, PSD-007 (5 and 10 mg/kg) was injected intravenously into the mice, and the tumor site was irradiated with laser light 6 hours after injection. Seven days after PDT, the size and weight of the tumors were measured. The inhibition rate of tumor was calculated, and all tumor specimens were taken for pathologic examination. After the diameter of tumor was 10-12 mm, the tumors were performed a marginal resection and subsequently followed 3 different treatments: without PDT (control), PDT with 240 J/cm2 or 360 J/cm2 laser irradiation. After 4 weeks treatment, the tumor recurrence rates were analyzed. Results MTT assay revealed that the cytotoxic effect of PDT on the LM-8 cells was positively correlated with the concentration of PSD-007 and the level of laser irradiation. When the concentration exceeded 4μg/ml, and the energy exceeded 6 J/cm2, the inhibition ratio was over 50%. No anti-tumor effect was observed in the cells treated with only laser irradiation or PSD-007 injection. Compared with the control group, the size and weight of the tumors were obviously decreased after PDT. PDT performed after marginal resection of the tumor reduced the rate of local recurrence. Conclusion PDT with PSD-007 showed cytotoxic effect on the LM-8 cells, and which performed after marginal resection of the tumor reduced the rate of local recurrence.     

Photodynamic therapy as palliation for esophageal cancer: experience in 215 patients

BACKGROUND: Photodynamic therapy (PDT) utilizes a photosensitizing agent, light, and oxygen to endoscopically ablate cancer cells. This review summarizes our experience with PDT for the palliation of bleeding or obstructing esophageal cancer (EC). METHODS: All patients with bleeding or obstructing EC treated with PDT from November 1996 through June 2002, were reviewed. After Photofrin II injection, nonthermal light treatment was delivered endoscopically. Dysphagia scores, duration of palliation, reinterventions, complications, and survival after treatment were reviewed. RESULTS: A total of 215 patients underwent 318 courses of PDT for bleeding (n = 15), obstruction (n = 277), bleeding and obstruction (n = 18), or other indications (n = 8). Tumor histology included 179 adenocarcinomas, 33 squamous cell carcinomas, and 3 undifferentiated. Seventy-five percent of EC were in the distal esophagus. In 85% of courses for obstruction, mean dysphagia scores improved pre- and post-PDT. The mean dysphagia-free interval was 66 days. Supplemental nutrition was discontinued after PDT in 8 of 27 patients (30%). Thirty-five patients required stent placement after PDT with a mean interval to reintervention of 58.5 days. PDT complications included perforation (2% of treatment courses), stricture (2%), Candida esophagitis (2%), pleural effusions (4%), and sunburn (6%). The procedure-related mortality rate was 1.8%, and median survival was 4.8 months. CONCLUSIONS: PDT offers effective palliation for patients with obstructing EC in 85% of treatment courses. The ideal EC patient for PDT palliation has an obstructing endoluminal cancer. Patients living more than 2 months may require reintervention to maintain palliation of malignant dysphagia, and a multimodality treatment approach is common.     

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.     

Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens

BACKGROUND AND OBJECTIVES: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. STUDY DESIGN/MATERIALS AND METHODS: A dorsal skinfold window chamber was installed surgically on female Sprague-Dawley rats. One milligram per kilogram of BPD solution was administered intravenously via a jugular venous catheter. Evaluated interventions were: control (no BPD, no light), PDT alone (576 nm, 16 minutes exposure time, 15 minutes post-BPD injection, 10 mm spot), PDL alone at 7 J/cm2 (585 nm, 1.5 ms pulse duration, 7 mm spot), PDL alone at 10 J/cm2, PDT/PDL (PDL at 7 J/cm2), and PDT/PDL (PDL at 10 J/cm2). To assess changes in microvascular blood flow, laser speckle imaging was performed before, immediately after, and 18 hours post-intervention. RESULTS: Epidermal irradiation was accomplished without blistering, scabbing or ulceration. A reduction in perfusion was achieved in all intervention groups. PDT/PDL at 7 J/cm2 resulted in the greatest reduction in vascular perfusion (56%). CONCLUSIONS: BPD PDT can achieve safe and selective vascular flow reduction. PDT/PDL can enhance diminution of microvascular blood flow. Our results suggest that PDT and PDT/PDL should be evaluated as alternative therapeutic options for treatment of hypervascular skin lesions including port wine stain birthmarks.     

血卟啉衍生物光动力作用杀伤人胰腺癌细胞的实验研究

目的 探讨光动力作用（ＰＤＴ）对体外培养的人胰腺癌细胞的杀伤效应。方法 以２株人胰腺癌细胞系Ｐ３和ＳＷ１９９０为研究对象,采用血卟啉衍生物（ＨＰＤ）作为光敏剂,用高压钠灯（功率密度２５ｍＷ／ｃｍ＾２）为光源,以系列深度的ＨＰＤ经不同剂量的光照后,用ＭＴＴ法测定ＰＤＴ对胰腺癌细胞的相对抑制率。结果 随光敏剂浓度的升高和照光剂的增加,光动力作用对细胞的相对抑制率逐渐增大,在低光动力剂量下明显上升,随后     

Green light photodynamic therapy in the human bladder

We conducted this pilot clinical study to investigate the safety, primarily acute toxicity, of green light (514.5 nm) whole bladder photodynamic therapy (PDT) in human bladders with transitional cell carcinoma. We enrolled five patients who were scheduled to undergo radical cystectomy and urinary diversion for locally muscle invasive bladder cancer. Four patients received intravenous injection of Photofrin at 1 mg/kg, while one patient received no drug, 48 hr before undergoing green light whole bladder photoactivation with light doses of 20-60 J/cm 2. Each patient underwent radical cystectomy on day 7 following light treatment. Post-PDT evaluation included daily monitoring of voiding symptoms, cystometric measurements of bladder capacity, and gross and histopathologic examination of the excised bladders. Our results show that the intensity of acute bladder irritation and acute post-PDT loss in bladder volume depended on the light dose and extent of bladder tumor with the associated inflammation. There was no transmural bladder injury and no treatment related morbidity. These data on acute toxicity suggest that green light whole bladder PDT treatment with 1 mg/kg of Photofrin and 20-40 J/cm 2 of laser power is safe.     

Safety studies for intraoperative photodynamic therapy

A new adjunctive therapy is needed for colorectal carcinoma surgery to decrease local recurrence rates. Photodynamic therapy (PDT) may be able to fulfil this role by activating the selective photosensitizer haematoporphyrin derivative (HPD) intraoperatively with laser light. This technique would necessitate the irradiation of normal tissues and therefore safety studies have been carried out in miniature pigs. Animals were photosensitized with HPD (5 mg kg⁻¹), then 48 h later colonic anastomoses and ureters were irradiated with 50 J cm⁻² of 510 nm-equivalent light. Anatomical, physiological and biochemical analyses were carried out, investigating both structure and function. Our results show that PDT applied in a potentially useful biological dose has no detrimental effect on the healing of anastomoses and ureteric structure and function. This work paves the way for intraoperative adjunctive PDT to be used effectively in man.     

A comparison of nalbuphine and pethidine for postoperative pain relief after orthopaedic surgery

Nalbuphine hydrochloride (Nubain; Du Pont Pharmaceuticals), a synthetic agonist-antagonist analgesic, in a dose of 20 mg was compared with pethidine 100 mg in 60 patients after elective surgery in a random double-blind study. Both drugs were given intramuscularly on the first day after surgery. The pain intensity and visual analogue scales would seem to indicate that nalbuphine has a longer duration of action than pethidine (P less than 0,05). The respiration rates in the pethidine group were significantly more depressed 30 minutes after the injection than in the nalbuphine group (P less than 0,05). Nalbuphine caused less depression of both systolic and diastolic blood pressure at both 30 and 60 minutes (P less than 0,001). The results of the study show that nalbuphine, in the dose used here, may prove to be a useful substitute for pethidine.