Evaluation of Antitumor Efficiency of Experimental Interstitial Photodynamic Therapy on the Model of M1 Sarcoma

Antitumor efficiency of interstitial photodynamic therapy was evaluated in experiments on outbred albino rats with implanted M-1 sarcoma. Interstitial photodynamic therapy was carried out using one diffusor at different output power and duration of exposure. The percentage of complete regression of the tumors increased with increasing exposure parameters.     

In vivo measurement of the optical interaction coefficients of human tumours at 630 nm

The light distribution within a treatment volume is determined by the source geometry (e.g. superficial or interstitial illumination) and the optical interaction coefficients of the irradiated tissue. We have measured the energy fluence rate at various points within tumours undergoing irradiation with 630 nm light for photodynamic therapy for several source geometries. The relative positions of source and detector fibres were determined using CT scanning techniques. The results of the measurements were then applied to solutions of the diffusion theory which allowed the determination of the absorption coefficient (sigma a = 30.5 +/- 16 m-1), the reduced scattering coefficient (sigma' s = 941 +/- 735 m-1), the effective attenuation coefficient (sigma eff = 261 +/- 49 m-1) and the build-up coefficient which relates surface irradiance to the energy fluence rate at depth (k = 1.6 +/- 0.6). Knowledge of these coefficients allows the transmission of light through tissue to be predicted and hence the optical dosimetry of subsequent treatments to be planned more effectively.     

生物组织内三维光动力学传输过程的Monte Carlo模拟方法

目的探讨激光在组织中的传输规律，为光动力学治疗计划的制定打下基础。方法建立可同时求解生物组织内三维激光场、光敏剂浓度场及温度场发展过程的Monte Carlo计算方法，以临床上常见的甲状腺癌的治疗过程为例进行模拟。结果两种典型激光照射方式即从光纤端面或侧面出射所引起的光动力学反应和热效应分布存在明显不同，在临床上有不同价值。结论计算结果有助于更好地理解光动力学治疗中组织内的基础光热质传输机制，本文方法为光动力学治疗计划的拟定建立了相对完整的理论基础。     

System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer

The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J∕cm2.     

In vivo measurement of parameters of dosimetric importance during interstitial photodynamic therapy of thick skin tumors

A system for interstitial photodynamic therapy is used in the treatment of thick skin tumors. The system allows simultaneous measurements of light fluence rate, sensitizer fluorescence, and tissue oxygen saturation by using the same fibers as for therapeutic light delivery. Results from ten tumor treatments using delta-aminolevulinic acid (ALA)-induced protoporphyrin IX show a significant, treatment-induced increase in tissue absorption at the therapeutic wavelength, and rapid sensitizer photobleaching. The changes in oxy- and deoxyhemoglobin content are monitored by means of near-infrared spectroscopy, revealing a varying tissue oxygenation and significant changes in blood volume during treatment. These changes are consistent with the temporal profiles of the light fluence rate at the therapeutic wavelength actually measured. We therefore propose the observed absorption increase to be due to treatment-induced deoxygenation in combination with changes in blood concentration within the treated volume. A higher rate of initial photobleaching is found to correlate with a less pronounced increase in tissue absorption. Based on the measured signals, we propose how real-time treatment supervision and feedback can be implemented. Simultaneous study of the fluence rate, sensitizer fluorescence, and local tissue oxygen saturation level may contribute to the understanding of the threshold dose for photodynamic therapy.     

光动力疗法联合钬激光治疗尖锐湿疣的疗效与安全性

目的：旨在研究光动力疗法联合钬激光治疗尖锐湿疣的疗效与安全性。方法：采用光动力疗法和钬激光疗法治疗尖锐湿疣120例,根据治疗方法将其分为3组：钬激光治疗组、光动力疗法组和联合治疗组,每组40人,对其治疗后的效果、不良反应及后续复发情况进行统计分析,比较3种方案治疗尖锐湿疣的效果与安全性。结果：治疗后联合治疗组的效果显著优于另外两组,钬激光治疗组与光动力治疗组之间差异无统计学差异。在治疗和随访过程中,3组之间均未出现明显不良反应。在治疗随访6个月后显示联合治疗组的复发率为10%,光动力治疗组复发率为17.5%,钬激光治疗组复发率为30%,3组之间差异具有统计学意义（P=0.001）。结论：光动力疗法联合钬激光是一种治疗尖锐湿疣安全、有效、快速的方法。     

Clinical Application of Photodynamic Therapy

Photodynamic therapy（PDT） is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy. PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called “singlet oxygen”. Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die. Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless. As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues. Hence ,there is selective targeting of the cancer and sparing of surrounding tissues. 3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgicaily（eg. ,the upper bronchi of the lung） ,PDT can still treat the site. 4. PDT is repeatable. Uniike radiation therapy,PDT can be used again and again. Hence,it offers a means of longterm management of cancer even if complete cure is not attainable.     

纯氧及LED阵列光动力复合治疗设备的研制

基于变压吸附制氧原理产生纯氧,并采用微透镜阵列多光谱LED发光器件与二次透镜阵列相结合构成光动力治疗辐照器,研制一种纯氧及LED阵列光动力复合治疗设备。其辐照器输出纯氧浓度大于90%,照射光包括波长625 nm红光、465 nm蓝光和520 nm绿光,应用光排序辐照技术实现纯氧及多光谱光动力复合治疗。通过辐照器上纯氧和照射光同步输出等多种外源性给氧保持光动力治疗区域的富氧状态,解决由于乏氧影响光动力疗效的问题。辐照器光学系统解决现有技术采用LED阵列排布替代激光器作为光动力治疗光源时存在的光能利用率低、光功率密度分布不均匀、不同波长光束在目标靶面光功率密度分布曲面差异大等缺陷。     

Development and characterization of multi-sensory fluence rate probes

Multi-sensory fluence rate probes (MSPs) yield several simultaneous measurements of photodynamic therapy (PDT) treatment light fluence from a single interstitial probe. Fluorescent sensors are embedded at desired positions along the axis of the optical fibre. A single fluorescence emission spectrum is obtained and decomposed using a partial least squares (PLS)-based analysis to yield the fluence at each sensor's location. The responsivity, linearity and possible photodegradation of each fluorophore chosen for the MSPs were evaluated using single-sensor probes. The performance of two- and three-sensor MSPs was evaluated experimentally. Individual fluorescence spectra collected from each sensor on the MSP were used to construct the training set necessary for the PLS-based analysis. The MSPs' responsivity, spatial resolution and accuracy were evaluated relative to a single scattering-tip detector. Three-fluorophore MSPs permitted three simultaneous measurements of the fluence rate gradient in a tissue-like phantom, with an average accuracy of 6.7%. No appreciable photodegradation or cross-talk was observed.     

Combined Exposure to Electrochemical Lysis and Photodynamic Therapy

A combination of electrochemical lysis and photodynamic therapy were used to attain complete resorption of M-1 sarcoma in rats; both treatment modalities were used with minimum parameters. Fotolon served as the photosensitizer for photodynamic therapy. Accumulation of the sensitizer in the tumor and normal tissue was evaluated before photodynamic therapy. Complete resorption of sarcoma in 100% cases (vs. photodynamic monotherapy) was attained only by the following treatment protocol: fotolon injection 50 min before electrochemical lysis (10 min) followed by photodynamic therapy. No tumor tissue was detected in morphological sections. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 95-98, January, 2009     

Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes for high/low power density photodynamic therapy

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm² for 0.5 min; low light dose = 25 mW/cm² for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors.     

The lack of sustained effect of bright light, after discontinuation, in non-seasonal major depression

BACKGROUND: Recently accumulated evidence has demonstrated that bright-light therapy in combination with antidepressants is effective in patients with non-seasonal major depression. Whether bright light has a sustained effect after discontinuation is, however, poorly investigated. METHOD: In this double-blind randomized study we report the results from a 4-week follow-up period in patients with major non-seasonal depression who had been treated for 5 weeks with sertraline combined with bright-light therapy or sertraline combined with dim-light therapy. At the beginning of the follow-up period the light therapy was stopped while sertraline treatment continued for 4 weeks. RESULTS: Depression scores decreased substantially in both groups, resulting in high response and remission rates in both groups after 9 weeks of treatment. The difference in depression scores at week 5, favouring the bright-light-treated group, disappeared gradually in the 4-week follow-up period, resulting in similar end-point scores. CONCLUSIONS: Bright light did not have a sustained effect after discontinuation. The offset of effect was complete after 4 weeks.     

Integrating spheres for improved skin photodynamic therapy

The prescribed radiant exposures for photodynamic therapy (PDT) of superficial skin cancers are chosen empirically to maximize the success of the treatment while minimizing adverse reactions for the majority of patients. They do not take into account the wide range of tissue optical properties for human skin, contributing to relatively low treatment success rates. Additionally, treatment times can be unnecessarily long for large treatment areas if the laser power is not sufficient. Both of these concerns can be addressed by the incorporation of an integrating sphere into the irradiation apparatus. The light fluence rate can be increased by as much as 100%, depending on the tissue optical properties. This improvement can be determined in advance of treatment by measuring the reflectance from the tissue through a side port on the integrating sphere, allowing for patient-specific treatment times. The sphere is also effective at improving beam flatness, and reducing the penumbra, creating a more uniform light field. The side port reflectance measurements are also related to the tissue transport albedo, enabling an approximation of the penetration depth, which is useful for real-time light dosimetry.     

Near-IR-triggered photothermal/photodynamic dual-modality therapy system via chitosan hybrid nanospheres

Gold nanorods (AuNR)- and indocyanine green (ICG)-encapsulated chitosan hybrid nanospheres (CS-AuNR-ICG NSs) were successfully prepared and used for photothermal and photodynamic combined therapy with a single irradiation. These nanospheres were characterized by transmission electron microscopy, dynamic light scattering and UV–Vis absorption spectra. The in vivo anticancer effects of the hybrid nanospheres were examined by photodynamic therapy (PDT), photothermal therapy (PTT), and PTT/PDT combined therapy. It was found that the hybrid nanospheres had spherical size of 180 nm and a broad adsorption from 650 nm to 900 nm. The spherical chitosan matrix could effectively load ICG and protect it from the rapid hydrolysis. In vivo near-infrared fluorescence imaging and biodistribution demonstrated that ICG and AuNR could be selectively delivered to the tumor site with high accumulation. With the irradiation by 808 nm laser, chitosan hybrid nanospheres were capable to simultaneously produce sufficient hyperthermia and reactive oxygen species to kill cancer cells at irradiation sites, resulting in the complete tumor disappearance in the most of tumor-bearing mice. Compared with photothermal therapy or photodynamic therapy alone, the combined therapy had a significantly synergistic effect and improved the therapeutic efficacy.     

喜泊分介导的光动力对大鼠泌乳素瘤MMQ细胞作用的研究

目的观察喜泊分介导的光动力对大鼠泌乳素瘤MMQ细胞的作用。方法不同浓度（0、5、10、20μg／mL）的喜泊分与细胞孵育3h后,先用405am波长紫外光照射观察细胞对喜泊分的吸收情况,然后用630nm波长红光照射不同时间（0、100、500、1000s）,采用MTr比色法测定细胞的增殖情况并计算抑制率;应用最大抑制率的参数光动力作用后,在倒置显微镜下观察细胞形态的变化,台盼蓝染色观察细胞的存活情况,Hoechst33342染色观察细胞凋亡或坏死的情况,Annexin／PI双染色流式细胞术分析细胞的死亡形式。结果喜泊分与MMQ细胞孵育3h后,用紫外光照射细胞,细胞激发出红光,说明MMQ细胞对喜泊分吸收良好;随着喜泊分浓度的增加与光照时间的延长,喜泊分-光动力对MMQ细胞的抑制率逐渐升高,当喜泊分浓度为20μg／mL、光照时间为1000s时,抑制率达到最高,为84％;应用最大抑制率的参数光动力作用后,细胞开始游离、细胞膜破裂,并出现很多细胞碎片;台盼蓝染色显示光动力导致MMQ细胞大量死亡;Hoechst33342染色显示喜泊分-光动力组MMQ细胞蓝色荧光强度明显增加,光动力导致细胞核固缩,细胞质凝集;Annexin／PI双染色流式细胞术结果分析显示．在喜泊分浓度为20μg／mL、光照时间为1000s时,死亡细胞主要是坏死细胞,达到92．3％。结论喜泊分介导的光动力对大鼠泌乳素瘤MMQ细胞具有光动力杀伤效应,可以引起显著的死亡。     

PDT combined with Intravesical BCG instillation would form an autovaccine for bladder cancer?

Bladder cancer is the second most common urologic malignancy after prostate cancer. Intravesical BCG as a treatment of superficial bladder cancer (SBC) has been used by urologists for over 30 years. Recently, photodynamic therapy (PDT), which uses a red laser and a photosensitive drug to destroy cancer cells, has been showed encouraging results in SBC treatment. However, BCG and PDT are applied to treatment of SBC alone. Currently, cancer vaccines are made in vitro. Several studies confirmed that tumour cells treated in vitro by PDT can be used for generating potent cancer vaccines, which were more effective than other modes of creating whole tumor vaccines, i.e., UV or ionizing irradiation [Gollnick SO, Vaughan L, Henderson BW. Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res 2002;62:1604–8]. Moreover, BCG is a pleiotropic immune stimulator oriented to cellular immunity. We thought that: after PDT destroyed targeted tumor cells on a large scale, Intravesical BCG could elicit and amplify the immune responses, which would directly form an in situ autovaccine in vivo against the primary tumor and metastases at distant sites. In this paper, we propose that the combination of Intravesical BCG and PDT would be a promising new modality for bladder cancer.     

内镜光动力微创疗法在胆管癌治疗中的作用

目的探讨内镜光动力微创疗法(PDT)在胆管癌治疗中的作用。方法对本院于2005年10月至2007年4月在常规综合治疗的基础上,开展内镜下的光动力微创治疗的15例胆管癌患者的相关临床资料进行回顾性总结分析。结果15例患者在PDT治疗后均取得良好效果,治愈3例,好转12例,除1例出现光敏性皮炎、3例出现术后胆道感染外,均未出现严重并发症。至目前为止,仍存活10例,中位生存期达243d(163~575d)。在随访期患者保持稳定的生活质量。结论内镜光动力联合微创治疗在胆管癌综合治疗中,具有创伤少、疗效好、并发症少的特点,对于提高胆管癌综合治疗的效果,提高生活质量及延长患者的生存期有重要的临床意义。     

光动力学疗法治疗癌症

光动力学疗法(photodynamic thempy，PDT)是一种非手术、浸入性极小的治疗方法，其应用分为两个阶段，即首先静脉注射一种光敏剂，然后以冷激光辐照激活药物，进行治疗。     

Light dosimetry for multiple cylindrical diffusing sources for use in photodynamic therapy

Since prostatic carcinoma is usually multifocal within the prostate, effective photodynamic therapy (PDT) of prostatic carcinoma is expected to require the photochemical destruction of the entire organ. Accurate light dosimetry will be essential to avoid damage to proximal sensitive tissue such as the rectum. The prostate will be illuminated using interstitial cylindrical fibreoptic light sources and, because of the limited transparency of prostate tissue, these sources will be mounted in a parallel array analogous to the source array used in brachytherapy. Both source spacing and the light delivered to each source will control light dosimetry from a parallel array of fibreoptic sources implanted into tissue. Clinical PDT will require dose planning in order to determine the position and illumination of each source prior to treatment, but unfortunately few methods of predicting light fluence from cylindrical interstitial sources currently exist. In this paper, a novel light fluence model is used to predict tissue transillumination resulting from cylindrical interstitial sources. The cylindrical source is modelled as a finite array of infinitesimal small sources using Christian Huygens' famous single-slit diffraction model. We show that this source model when combined with a robust derivation of fluence in a spherical geometry using diffusion theory, accurately predicts fluence levels from a single cylindrical source in a variety of media. This method is found to retain its accuracy near the sources. With a simple extension, this fluence model is used to predict the light fluence levels from an array of three sources and the predicted fluence is found to compare favourably with experimental data.     

Role of Laser Energy Density for Photodynamic Therapy of Radiation Injuries of the Skin

The role of different laser energy densities used in photodynamic therapy in the reparation of radiation ulcers caused by X-ray exposure in a dose of 80 Gy was studied. Tissue reparation manifested differently at different laser energy densities. After photodynamic therapy at energy density of 0.1 J/cm² the rate of healing was notably higher during early periods. After exposure at 5 and 40 J/cm² acceleration of ulcer healing was observed 14 and more days after the treatment, indicating the emergence of another mechanism of photodynamic therapy effect. Laser energy density of 5 J/cm² was the most effective for maximally complete healing of radiation ulcers. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 570–573, November, 2005