Photodynamic laser cyclodestruction with chloroaluminum sulfonated Phthalocyanine (CASPc) or photofrin®(PII) Vs. Nd:YAG laser cyclodestruction in a pigmented rabbit model

Background and Objective: To investigate Photofrin® (PII) and CASPc for photodynamic therapy (PDT) of the ciliary body in rabbits. Study Design/Materials and Methods: PII (10 mg/kg) or CASPc (1 mg/kg) was given by ear vein. Pharmacokinetics were studied in frozen sections by fluorescence microscopy (CCD camera based low light detection system with digital image processing) at 1 and 24 h (8 rabbits;16 eyes). Laser light was delivered (argon pumped dye laser;630 and 675 nm;8 rabbits;16 eyes) by contact fiberoptic. To compensate for iris attenuation, irradiance was 125 mW/cm² (20, 40, 80, or 160 J/cm²). Controls (4 rabbits;8 eyes) received laser light without photochemicals (OD) and for comparison, continuous wave Nd:YAG laser by fiberoptic (0.8–1.2J;OS). Results: Localization studies showed intravascular distribution with some selective ciliary body distribution at 24 h (PII > CASPc). Rabbits treated with PII or CASPc exhibited variable amounts of gross ciliary body edema, infarction, and necrosis by 24–48 h. This response was not seen in PDT control tissues;damage was seen in the iris and ciliary body, with partial vacuolization of the pigment epithelium. Conclusion: PDT may offer a more selective approach to ciliary body destruction. A small but significant thermal effect was seen during PDT from melanin photon uptake with damage to iris and ciliary body. Thermal damage and potential interaction with ocular visual pigments may limit use of these photochemicals and wavelengths for PDT of the ciliary body © 1995 Wiley-Liss, Inc.     

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.     

光动力学疗法与局部化疗联合治疗进展期食管贲门癌

作应用光动力学疗法（ＰＤＴ）对进展期食管贲门癌５５例进行治疗，并对其中１５例联合应用内镜下局部注射抗癌药物。对每一患均先静脉滴注血卟啉衍生物（ＨＰＤ）５ｍｇ／ｋｇ，于用药后２４，４８和７２ｈ分别用波长６３０ｎｍ的铜蒸汽激光照射肿瘤部位。联合治疗组除ＰＤＴ治疗外，于每次光照前肿瘤局部注射５－Ｆｕ２５０～５００ｍｇ。结果：联合治疗组的近期显效率高于单纯ＰＤＴ组（Ｐ〈０．０５）。病例随访６～１６月，     

Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

Successful treatment of periungual warts using photodynamic therapy: a pilot study

AIM: The aim of this pilot study was an investigation on photodynamic therapy (PDT) whether it is a good alternative for treating periungual and subungual warts of the hands. STUDY DESIGN: Twenty patients (mean age: 30.5 years) with a total of 40 periungual and subungual warts were treated with PDT. A photosensitizer, 20%delta-aminolevulinic acid was applied on the warts. After a mean incubation time of 4.6 h (SD: 1.2), the warts were irradiated with the VersaLight for 5-30 min (15.2 +/- 4.3 min). RESULTS: After a mean of 4.5 treatments a mean clearance of 100% was achieved in 90% of the patients. One patient (5%) showed a clearance of 50% and another showed no improvement. The subungual or periungual location of the wart had no influence on the number of treatments or end result (P > 0.05). There were two recurrences during the mean follow-up period of 5.9 months (SD: 7.6). Besides mainly pain and hyperpigmentation, most treatments had no side-effects. CONCLUSION: PDT can offer a good alternative for treating periungual warts of the hands. Larger studies are indicated.     

Dihematoporphyrin ether-induced photosensitivity in laryngeal papilloma patients

Twenty-six patients with recurrent laryngeal papillomatosis received 2.5 mg/kg of Dihematoporphyrin Ether (DHE) intravenously prior to photodynamic therapy. All patients experienced some degree of photosensitivity, the only known side effect of DHE. Reported reactions included mild erythema and inflammation (88%), swelling (58%), blistering (23%), ocular discomfort (61.5%), pruritus (38%), and skin hyperpigmentation (46%). Length of sensitivity ranged from 4-17 weeks, with an average duration of 9 weeks. No long-term debilitating sequelae were noted. Degree of skin reaction mainly depended on how compliant the patient was in following precaution instructions. Although restrictive precautions were often difficult to strictly adhere to, most patients felt the potential benefits of the therapy far outweighed any inconvenience.     

Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant-enhanced arthritis in MRL-lpr mice.

Although numerous experimental immunomodulatory regimens have been reported to be effective in the treatment of rheumatoid arthritis, they also produce undesirable side effects. An alternative specific modality of localized treatment is photodynamic therapy (PDT). In this study we treated 13-week-old MRL-lpr mice whose spontaneous arthritis was enhanced by intradermal injection of Freund's complete adjuvant (FCA). One group received transcutaneous photodynamic therapy at days 0, 10, and 20, following the FCA injection. The other groups were injected with 1 mg/kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA), or treated with 3 Gy sublethal whole body irradiation (WBI). The development of swelling was monitored for 1 month, at which time proteinuria, lymphadenopathy and the histopathology of the joints and kidneys were assessed. The results demonstrated that PDT and the conventional treatments significantly ameliorated swelling of the hindlimbs from 70% in the untreated FCA-injected animals to below the 19% level characteristic of the unmanipulated control. Histological examination showed a reduction in pannus formation, and cartilage and bone destruction, the characteristics of adjuvant-enhanced arthritis. PDT did not affect the survival rate, lymphoproliferation, or proteinuria of the treated animals. However, indomethacin increased proteinuria, and was less effective in preventing cartilage and bone destruction. Furthermore, lower doses of CsA and WBI exacerbated arthritis activity. These results indicate that photodynamic therapy can inhibit the development of adjuvant-enhanced arthritis in MRL-lpr mice with similar effectiveness to the conventional treatments, but without their negative side effects.     

癌光啉对动物移植瘤的光化学诊治作用

本文报道了肿瘤光化学诊治新药癌光啉(PsD-007)对三种动物移植瘤(S_(180)肉瘤、Lewis肺癌、U_(14)宫颈癌)的实验性光化学诊治效果,初步探讨了辐照光能量和药物剂量与肿瘤实验性诊治效果的关系。作者采用“透镜光阑”法改善辐射光斑内功率密度分布的不均匀性。提供了一种能比较客观地评价药物对动物移植瘤的光动力学治疗效价的模型体系。     

Intrauterine light delivery for photodynamic therapy of the human endometrium

Photodynamic therapy is currently being evaluated as a minimallyinvasive procedure for endometrial ablation not requiring anaesthesia.Light penetration depths at 630, 660 and 690 nm and the optimalconfiguration of intrauterine light-diffusing fibres were determinedin 14 human uteri to assist in the design of a light intrauterinedevice. Post-menopausal ex-vivo uteri showed a significantlylower light penetration depth than pre-menopausal uteri. Witha single central diffusing fibre inserted, the fluence ratemeasured in the uterine wall at the most remote point of thecavity decreased to 1.1 ± 0.4% of that measured at closestproximity, whereas it decreased to only 40.0 ± 9.0% withthree fibres. Distension of the uterine cavity with 2 ml ofan optically clear fluid increased the fluence rate at the fundusbetween the fibres at a depth of 2 mm by a factor of 4. We concludethat in normal-sized pre-menopausal uterine cavities, threediffusing fibres will deliver an optical dose above the photodynamicthreshold level at a depth of 4 mm, even in the most remoteareas, in <30 min without causing thermal damage. For distortedand elongated cavities, either slight distension of the cavityor the insertion of a fourth diffusing fibre is required.