Fluorescence and absorption assessment of a lipid mTHPC formulation following topical application in a non-melanotic skin tumor model

Although the benefits of topical sensitizer administration have been confirmed for photodynamic therapy (PDT), ALA-induced protoporphyrin IX is the only sensitizer clinically used with this administration route. Unfortunately, ALA-PDT results in poor treatment response for thicker lesions. Here, selectivity and depth distribution of the highly potent sensitizer meso-tetra(hydroxyphenyl)chlorin (mTHPC), supplied in a novel liposome formulation was investigated following topical administration for 4 and 6 h in a murine skin tumor model. Extraction data indicated an average [+/- standard deviation (SD)] mTHPC concentration within lesions of 6.0(+/-3.1) ngmg tissue with no significant difference (p<0.05) between 4- and 6-h application times and undetectable levels of generalized photosensitivity. Absorption spectroscopy and chemical extraction both indicated a significant selectivity between lesion and normal surrounding skin at 4 and 6 h, whereas the more sensitive fluorescence imaging setup revealed significant selectivity only for the 4-h application time. Absorption data showed a significant correlation with extraction, whereas the results from the fluorescence imaging setup did not correlate with the other methods. Our results indicate that this sensitizer formulation and administration path could be interesting for topical mTHPC-PDT, decreasing the effects of extended skin photosensitivity associated with systemic mTHPC administration.     

A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy

We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O2) consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT) in vivo. Previously published models have been improved by considering perfused vessels as a time-dependent 3O2 source and linking the 3O2 concentration in the vessel to that within the tissue through the Hill equation. The time-dependent photochemical 3O2 consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of 3O2 is provided for in the capillaries and in the surrounding tissue. A self-sensitized singlet oxygen (1O2)-mediated bleaching mechanism and the measured, initially nonuniform distribution of mesotetrahydroxyphenyl chlorin at 3 h after intravascular administration were used to demonstrate the capabilities of the model. Time-evolved distributions of 3O2 concentration were obtained by numerically solving two-dimensional diffusion-with-reaction equations both in the capillary and the adjacent tissue. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O2 saturation (SO2) within the vessels, irreversible sensitizer degradation due to photobleaching, and the microscopic distributions of 3O2, sensitizer concentration, and 1O2 dose deposition under various irradiation conditions. The simulations reveal severe axial gradients in 3O2 and in photodynamic dose deposition in response to a wide range of clinically relevant treatment parameters. Thus, unlike former Krogh cylinder-based models, which assume a constant 3O2 concentration at the vessel, this new model identifies conditions in which 3O2 depletion and minimal deposition of reacting 1O2 exist near the end of axial segments of vessels and shows that treatment-limiting 3O2 depletion is induced at fluence rates as low as 10 mW cm(-2). These calculations also demonstrate that intercapillary heterogeneity of photosensitizer contributes significantly to the distribution of photodynamic dose. This more rigorous mathematical model enables comparison with experimentally observable, volume-averaged quantities such as SO2 and the loss of sensitizer fluorescence through bleaching that have not been included in previous analyses. Further, it establishes some of the intrinsic limitations of such measurements. Specifically, our simulations demonstrate that tissue measurements of SO2 and of photobleaching are necessarily insensitive to microscopic heterogeneity of photodynamic dose deposition and are sensitive to intercapillary spacing. Because prior knowledge of intercapillary distances in tumors is generally unavailable, these measurements must be interpreted with caution. We anticipate that this model will make useful dosimetry predictions that should inform optimal treatment conditions and improve current clinical protocols.     

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: influence of photosensitizer formulation and tissue location

In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan? in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg? and Foslip?, on FDPS response was investigated. Furthermore, FDPS was evaluated in target organs for head-and-neck PDT. Fifty-four healthy rats were intravenously injected with one of the three formulations of mTHPC at 0.15 mg kg(-1). FDPS was performed on liver, tongue, and lip. The mTHPC concentrations estimated using FDPS were correlated with the results of the subsequent harvested and chemically extracted organs. An excellent goodness of fit (R(2)) between FDPS and extraction was found for all formulations in the liver (R(2)=0.79). A much lower R(2) between FDPS and extraction was found in lip (R(2)=0.46) and tongue (R(2)=0.10). The lower performance in lip and in particular tongue was mainly attributed to the more layered anatomical structure, which influences scattering properties and photosensitizer distribution.     

Vascular and cellular targeting for photodynamic therapy

Photodynamic therapy (PDT) involves the combination of photosensitizers (PS) with light as a treatment, and has been an established medical practice for about 10 years. Current primary applications of PDT are age-related macular degeneration (AMD) and several types of cancer and precancer. Tumor vasculature and parenchyma cells are both potential targets of PDT damage. The preference of vascular versus cellular targeting is highly dependent upon the relative distribution of photosensitizers in each compartment, which is governed by the photosensitizer pharmacokinetic properties and can be effectively manipulated by the photosensitizer drug administration and light illumination interval (drug-light interval) during PDT treatment, or by the modification of photosensitizer molecular structure. PDT using shorter PS-light intervals mainly targets tumor vasculature by confining photosensitizer localization within blood vessels, whereas if the sensitizer has a reasonably long pharmacokinetic lifetime, then PDT at longer PS-light intervals can induce more tumor cellular damage, because the photosensitizer has then distributed into the tumor cellular compartment. This passive targeting mechanism is regulated by the innate photosensitizer physicochemical properties. In addition to the passive targeting approach, active targeting of various tumor endothelial and cellular markers has been studied extensively. The tumor cellular markers that have been explored for active photodynamic targeting are mainly tumor surface markers, including growth factor receptors, low-density lipoprotein (LDL) receptors, transferrin receptors, folic acid receptors, glucose transporters, integrin receptors, and insulin receptors. In addition to tumor surface proteins, nuclear receptors are targeted, as well. A limited number of studies have been performed to actively target tumor endothelial markers (ED-B domain of fibronectin, VEGF receptor-2, and neuropilin-1). Intracellular targeting is a challenge due to the difficulty in achieving sufficient penetration into the target cell, but significant progress has been made in this area. In this review, we summarize current studies of vascular and cellular targeting of PDT after more than 30 years of intensive efforts.     

Effect of hypericin-mediated photodynamic therapy on the expression of vascular endothelial growth factor in human nasopharyngeal carcinoma

Photodynamic therapy (PDT) is currently being used as an alternative treatment modality for various types of cancers. PDT involves the selective uptake and retention of a photosensitizer in the tumor followed by light irradiation of an appropriate wavelength to cause the destruction of tumor cells by the formation of cytotoxic reactive oxygen species. The photosensitizer, hypericin, has shown great potential due to its light-dependent tumor destructive properties. However, as hypericin-mediated PDT primarily targets tumor vasculature, it induces certain pro-angiogenic factors such as vascular endothelial growth factor (VEGF) in the tumor tissue as a result of hypoxia. This study examines the role of hypericin-mediated photodynamic therapy in stimulating the expression of key angiogenesis growth factor VEGF in order to elucidate the process of tumor angiogenesis in nasopharyngeal carcinoma xenografts. We also investigated the effect of angiogenesis inhibitor celebrex on human VEGF levels when combined with hypericin-PDT. These studies were conducted on an in vivo human nasopharyngeal xenograft model. VEGF was measured in the control and hypericin-PDT treated tumors. VEGF levels were found to be higher when the tumors were treated at a 1-h drug-light interval compared to a 6-h interval, due to extensive vascular damage. At 72 h post hypericin-PDT, VEGF levels were upregulated indicating the initiation of regrowth in tumors. The use of angiogenesis inhibitor, celebrex, along with hypericin-PDT downregulated the human VEGF levels suggesting that angiogenesis inhibitors can be used to improve the outcome of hypericin-PDT in nasopharyngeal carcinomas.     

New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm

To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.     

光动力治疗中激光辐射有效吸收剂量

光动力治疗中激光辐射有效吸收剂量郑蔚谢树森（福建师范大学激光研究所，福州３５０００７）ＡｂｓｔｒａｃｔＲｅｓｅａｒｃｈｅｒｓｔｙｐｉｃａｌｙｕｓｅｒａｄｉａｎｔｅｘｐｏｓｕｒｅｏｎｔｈｅｓｕｒｆａｃｅｏｆｔｉｓｕｅｔｏｅｖａｌｕａｔｅｔｈｅｌｉｇｈｔ...     

Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion

We investigated the feasibility of using optical coherence tomography (OCT) for noninvasive real-time visualization of the vascular effects of photodynamic therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements were initially performed after administrating vaso-active drugs or clamping of the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). Tumors were illuminated using either a short drug light interval (D-L, 3 h), when mTHPC is primarily located in the tumor vasculature or a long D-L interval (48 h), when the drug is distributed throughout the whole tumor. OCT enabled visualization of the different layers of tumor, and overlying skin with a maximal penetration of < or =0.5-1 mm. PDT with a short D-L interval resulted in a significant decrease of perfusion in the tumor periphery, to 20% of pre-treatment values at 160 min, whereas perfusion in the skin initially increased by 10% (at 25 min) and subsequently decreased to 60% of pre-treatment values (at 200 min). PDT with a long D-L interval did not induce significant changes in perfusion. The concept of using noninvasive OCT measurements for monitoring early, treatment-related changes in morphology and perfusion may have applications in evaluating effects of anti-angiogenic or antivascular (cancer) therapy.     

Perylenequinones in photodynamic therapy: cellular versus vascular response.

Photodynamic therapy (PDT) is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about molecular oxygen-induced cell death. We have investigated the efficacy of photosensitizers from the family perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of cancer. These photosensitizers are known as potent second generation natural photosensitizers that have phototherapeutic advantages over the presently used porphyrins. We have studied the in vitro signaling mechanism involved in the photodynamic action following PDT in various human carcinoma cell lines. The difference of tumor cell death between two modes of action i.e., vascular- and cellular-mediated cell death, were evaluated in order to compare treatments that can efficaciously eradicate tumor in xenografts model. The antivascular effect of PDT was demonstrated in the chick chorioallantoic membrane (CAM) model. Tumor therapy based on targeting the vasculature of the tumor is indeed promising as demonstrated in the higher relative regression percentage of treated tumor compared to cellular targeted PDT. The favorable tumor response derived from short drug-light interval mediated PDT was primarily based on the differential uptake of the photosensitizer into tumor-associated vasculature as opposed to the cellular compartments of the tumor.     

Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer.

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.     

Oxygen diffusion and reaction kinetics in the photodynamic therapy of multicell tumour spheroids

Effects of oxygen diffusion and reaction kinetics in photodynamic therapy are considered in the context of a multicell tumour spheroid model. Steady-state measurements of oxygen made with a Clark-style microelectrode (4 microm diameter tip) enable us to determine the rate of metabolic oxygen consumption and the oxygen diffusion coefficient in 500 microm diameter EMT6/Ro spheroids. These values are 5.77 micromol 1(-1) s(-1) and 1460 microm2 s(-1), respectively. Time-dependent electrode measurements of oxygen concentration during laser irradiation of individual Photofrin-sensitized spheroids are fitted to numerical solutions of a pair of diffusion-with-reaction equations. The analysis yields the rate of photodynamic oxygen consumption and a parameter that governs the oxygen sensitivity of photodynamic therapy. These experimentally derived quantities are used to calculate the temporal and spatial distributions of oxygen and the rate of oxygen consumption in a spheroid during irradiation at several fluence rates. The spatial distribution of photodynamic oxygen consumption is strongly fluence rate dependent. Using the experimental and theoretical results developed in this report, previously published survival data are analysed. The analysis indicates that the threshold dose of reacting singlet oxygen in the EMT6/Ro spheroid is 323 +/- 38 micromol 1(-1) (mean +/- SEM).     

Comparison of merocyanine 540-mediated photodynamic action on leukemia cells between pulsed and continuous wave light sources.

Whether a pulsed laser is superior to a continuous wave (CW) light source in photodynamic therapy (PDT) of cancer is still unclear and contradictory in the literature. Although photosaturation of a sensitizer and oxygen depletion in tumor have been considered to be involved during pulsed laser irradiation, there is a lack of experimental data. In the present work several parameters such as the amount of merocyanine 540 (MC540) in cells, the oxygen concentration in cells, and the amount of photos reaching cells during pulsed laser irradiation, were studied to compare the MC540-mediated PDT effects of a pulsed laser and a CW light source on murine myeloid WEH-3B (JCS) cells in vitro. The results showed that the pulsed laser was less effective at cell inactivation than the CW light under the same irradiation dose. However, when the energy of the pulsed laser was reduced from 0.25 to 0.06 mJ/cm2 while keeping the total irradiation dose unchanged, the photoinactivation of cells was increased significantly. Based on the measurements and calculations for the present experimental conditions, each cell has about 108 MC540 molecules bound (5 microg/ml MC540 for 1 hr) and receives about 109 photos from 0.25 mJ/cm2 of the pulsed laser. The results indicate that the photosaturation of MC540 occurs in the present conditions due to the fact that the photons received by one cell in one laser pulse were much more than the numbers of MC540 molecules bound to one cell. Thus, the photosaturation of the photosensitizer is one of the reasons to explain the different efficiency in cell inactivation between the pulsed laser and CW light.     

Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation

Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW∕cm(2), 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.     

Influence of uterine cervix shape on photodynamic therapy efficiency

The goal of practical photodynamic therapy (PDT) dosimetry is to optimize the distribution of a light dose delivered to tissue by selecting the irradiation time and geometry to match the geometry and optical properties of the tumor and surrounding tissue. Homogeneous irradiation is among one of the sources of correct PDT dosimetry. The goal of this study is to model and predict the influence of the shape of a treated organ in need of light dose correction. Thus efficiency of light delivery to the tissue volume is defined and calculated with shape factors of the uterine cervix as parameters. Two cases (parallel and divergent beam) of enlightening configuration are investigated. The calculations presented extend PDT dosimetry with the influence of the shape of the uterine cervix on PDT necrosis depth. This allows for photodynamic excitation light dose correction for more reliable treatments.     

Methylene blue-encapsulated phosphonate-terminated silica nanoparticles for simultaneous in vivo imaging and photodynamic therapy

A bifunctional nanoparticles-based carrier for simultaneous in vivo imaging and photodynamic therapy by encapsulating methylene blue (MB) alone in the phosphonate-terminated silica matrix has been developed. The phosphonate-terminated silica nanoparticles, entrapping water-soluble photosensitizer MB (MB-encapsulated PSiNPs), are synthesized by the controlled synchronous hydrolysis of tetraethoxysilane and trihydroxyl silyl propyl methyl phosphonate in the water-in-oil microemulsion. The resulting MB-encapsulated PSiNPs effectively prevent the leakage of entrapped MB from the particles and provide protection for against reduction by diaphorase. Enough dose of irradiation to the MB-encapsulated PSiNPs under the light of 635 nm results in efficient generation of singlet oxygen and induces photodynamic damage to Hela cells. Furthermore, the non-invasive visualization of MB-encapsulated PSiNPs in mice under the in vivo imaging system confirmed the MB-encapsulated PSiNPs also presents near-infrared luminescence for in vivo imaging. And the effect of the PDT toward the xenograft tumor in vivo is exciting after imaging the MB-encapsulated PSiNPs injected tumor using in vivo optical imaging system. Thus, the single particle platform is effective for simultaneous in vivo imaging and photodynamic therapy without using extra agent, which can provide image-guidance for site-specific photodynamic therapy.     

Fluorescence monitoring of a topically applied liposomal Temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies.

Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is a potent photodynamically active substance in clinical use today. Usually, the substance is given systemically and a known drawback with this administration route is a prolonged skin light sensitization. For the first time to our knowledge, a liposomal Temoporfin gel formulation for topical application was studied in connection with photodynamic therapy (PDT) of nonpigmented skin malignancies in humans. Intervals of 4 hr between drug administration and light irradiation were used. Sensitizer distribution within tumor and surrounding normal skin was investigated by means of point monitoring and imaging fluorescence spectroscopy before, during, and after PDT, showing high tumor selectivity. Furthermore, the bleaching of Temoporfin was studied during the PDT procedure by monitoring the fluorescence following excitation by using a therapeutic light. A 30-35% light-induced photometabolization was shown. No pain occurred during or after treatment. It was also observed that the treated area did not show any swollen tissue or reddening, as is often seen in PDT using topical delta-aminolevulinic acid. On controlling the patients one week after treatment, healing progress was observed in several patients and no complications were registered.     

Redox ratio of mitochondria as an indicator for the response of photodynamic therapy

The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.     

Chlorophyll derivatives (CpD) extracted from silk worm excreta are specifically cytotoxic to tumor cells in vitro

Among chlorophyll derivatives (CpD-A, -B, -C, and -D) extracted from silk worm (Bombyx mori) excretas, CpD-A was extensively studied to clarify its role as a "photosensitizer" for photodynamic therapy (PDT) of tumors in vitro. It was found that CpD-A was photoreactive both in itself and also in its cell bound forms. The cell bound CpD-A produced fluorescent light and singlet oxygen following the exposure to lights of varied wave length. Among them, lights of near 650 nm, which was the maximum absorbance band, efficiently activated CpD-A following the application of only 10 minutes of irradiation. CpD-A was found to have specificity for the human and mouse tumor cells regardless of their species difference. A higher intensity of fluorescence and a larger amount of CpD-A were found in the tumor cells as opposed to the intensity found in normal cells. Only 10 minutes of light irradiation of the CpD-A treated tumor cells resulted in their rapid and complete destruction within 2 hours of irradiation. Simultaneously, more than 80% of the normal human and mouse control cells remained alive after receiving treatment. These findings suggested that CpD-A produced by use of silkworm excreta could be used as a photosensitizer for PDT of tumors by the use of lights of near 650 nm.     

Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery.

To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.     

研究不同光敏剂诱导的光动力疗法对人白血病细胞的杀伤作用

目的 研究并比较3种卟啉类光敏剂——血卟啉衍生物(HpD)、癌光啉(PsD007)和血卟啉 单甲醚(HMME)诱导的光动力疗法(PDT)对白血病细胞K562的杀伤效应.方法 以人白血病细胞K562为研究对象,分为对照组和PDT组,以梯度浓度的光敏剂与K562细胞共同孵育,经不同能量光照后,用噻唑蓝(MTT)法测定PDT对K562细胞的杀伤作用.结果 与对照组相比,PDT对K562细胞有明显杀伤作用,并随着光敏剂浓度的增加和光照能量的增大,效果增强.PsD007-PDT和HMME-PDT的效果都明显优于HpD-PDT(P＜0.05);而当光敏剂质量浓度较大(25 μg/ml)或能量密度较大(7.2 J/cm2)时,PsD007-PDT的作用效果优于HMME-PDT.结论 PDT对人白血病细胞K562具有明显的杀伤作用,其对细胞的抑制率具有显著的剂量效应关系;PDT对K562的杀伤效应与光敏剂种类有关,HpD-PDT的杀伤效果不如PsD007和HMME;在较高能量密度和较大光敏剂浓度的条件下,PsD007-PDT的效果优于HMME-PDT.