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Light Dose (light + dose)
Selected AbstractsEvaluation of the Photosensitizer Tookad® for Photodynamic Therapy on the Syrian Golden Hamster Cheek Pouch Model: Light Dose, Drug Dose and Drug,light Interval Effects,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2003François Borle ABSTRACT We have evaluated the efficacy of the new photosensitizer (PS) Tookad® in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection,light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad® could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels. [source] Hypericin-mediated Photocytotoxic Effect on HT-29 Adenocarcinoma Cells Is Reduced by Light Fractionation with Longer Dark Pause Between Two Unequal Light DosesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2005Veronika Sa ABSTRACT The present study demonstrates the in vitro effect of hypericin-mediated PDT with fractionated light delivery. Cells were photosensitized with unequal light fractions separated by dark intervals (1 or 6 h). We compared the changes in viability, cell number, survival, apoptosis and cell cycle on HT-29 cells irradiated with a single light dose (12 J/cm2) to the fractionated light delivery (1 + 11 J/cm2) 24 and 48 h after photodynamic treatment. We found that a fractionated light regime with a longer dark period resulted in a decrease of hypericin cytotoxicity. Both cell number and survival were higher after light sensitization with a 6-h dark interval. DNA fragmentation occurred after a single light-dose application, but in contrast no apoptotic DNA formation was detected with a 6-h dark pause. After fractionation the percentage of cells in the G1 phase of the cell cycle was increased, while the proportion of cells in the G2 phase decreased as compared to a single light-dose application, i.e. both percentage of cells in the G1 and G2 phase of the cell cycle were near control levels. We presume that the longer dark interval after the irradiation of cells by first light dose makes them resistant to the effect of the second illumination. These findings confirm that the light application scheme together with other photodynamic protocol components is crucial for the photocytotoxicity of hypericin. [source] Photodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical ApplicationDERMATOLOGIC SURGERY, Issue 8 2000Arie Orenstein MD Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source] Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Ho-Kee Koon Abstract Epidermal growth factor receptor (EGFR), a receptor often expressed in nasopharyngeal carcinoma (NPC) cells, is one of the recently identified molecular targets in cancer treatment. In the present study, the effects of combined treatment of Zn-BC-AM PDT with an EGFR inhibitor AG1478 were investigated. Well-differentiated NPC HK-1 cells were subjected to PDT with 1,µM of Zn-BC-AM and were irradiated at a light dose of 1,J/cm2 in the presence or absence of EGFR inhibitor AG1478. Specific protein kinase inhibitors of downstream EGFR targets were also used in the investigation. EGFR, Akt, and ERK were found constitutively activated in HK-1 cells and the activities could be inhibited by the EGFR inhibitor AG1478. A sub-lethal concentration of AG1478 was found to further enhance the irreversible cell damage induced by Zn-BC-AM PDT in HK-1 cells. Pre-incubation of the cells with specific inhibitors of EGFR (AG1478), PI3k/Akt (LY294002), or MEK/ERK (PD98059) before light irradiation were found to enhance Zn-BC-AM PDT-induced formation of apoptotic cells. The efficacy of Zn-BC-AM PDT can be increased through the inhibition of EGFR/PI3K/Akt and EGFR/MEK/ERK signaling pathways in NPC cells. Combination therapy with Zn-BC-AM PDT and EGFR inhibitors may further be developed for the treatment of advanced NPC. J. Cell. Biochem. 108: 1356,1363, 2009. © 2009 Wiley-Liss, Inc. [source] Lethal photosensitization of periodontal pathogens by a red-filtered Xenon lamp in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2003Donco Matevski Background:, The ability of Helium,Neon (He,Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT). Objectives:, We investigated the potential of a conventional light source (red-filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials. Materials and methods:,Porphyromonas gingivalis 381 was used as the primary test bacterium. Results:, Treatment with a 2.2 J/cm2 light dose and 50 µg/ml TBO concentration resulted in a bacterial kill of 2.43 ± 0.39 logs with the He,Ne laser control and 3.34 ± 0.24 logs with the lamp, a near 10-fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 ± 0.68 logs kill). Conclusions:, The data indicate that PDT utilizing a conventional light source is at least as effective as laser-induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 µg/ml TBO. [source] Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2006A randomized, double-blind phase I/II study Abstract Background, Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. Objective, A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. Methods, In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm2 and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). Results, The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. Conclusion, Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile. [source] The Neovessel Occlusion Efficacy of 151 -Hydroxypurpurin-7-Lactone Dimethyl Ester Induced with Photodynamic TherapyPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2010Siang Hui Lim In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 151 -hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 ,L volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 ,g per embryo of G2 and a light dose of 20 J cm,2 at a fluence rate of 40 mW cm,2 filtered at 400,440 nm,a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light,an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer. [source] Fluorescence Kinetics of Protoporphyrin-IX Induced from 5-ALA Compounds in Rabbit Postballoon Injury Model for ALA-PhotoangioplastyPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2008Oh-Choon Kwon Protoporphyrin IX (PpIX) is one of the photodynamically active substances that are endogenously synthesized in the metabolic pathway for heme as a precursor. Aminolevulinic acid-esters are more lipophilic than conventional 5-aminolevulinic acid (ALA) and some of them are currently being approved as new drugs for photodynamic diagnosis (PDD) and photodynamic therapy (PDT). In order to investigate the pharmacokinetics of ALA and ALA-ethyl ester (ALA-ethyl) in the atheromatous plaque and normal aortic wall of rabbit postballoon injured artery, each 60 mg kg,1 of ALA or ALA-ethyl was injected intravenously followed by serial detection of PpIX fluorescence of harvested arteries at 0,48 h post-injection. Maximum PpIX build-up in the atheromatous plaque was seen at 2 h after injecting ALA. In contrast, it occurred at 9 h after injecting ALA-ethyl. In addition, the selective build-up of ALA in the atheromatous plaque compared to normal vessel wall was much higher (10 times) than that of ALA-ethyl. The time of maximum fluorescence intensity of PpIX was employed as drug-light-interval for subsequent PDT treatment of the atheromatous plaque with 50,150 J cm,1 of light dose. Significant reduction in plaque was observed without damage of the medial wall at both groups, but smooth muscle cell (SMC) was still present in the media region below the PDT-treated atheromatous plaque. In conclusion, ALA may be a more effective compound for endovascular PDT treatment of the atheromatous plaque compared with ALA-ethyl based on their pharmacokinetics, but further optimization of PDT methodology remains to remove completely residual SMC in the media for preventing potential restenosis. [source] Hypericin-mediated Photocytotoxic Effect on HT-29 Adenocarcinoma Cells Is Reduced by Light Fractionation with Longer Dark Pause Between Two Unequal Light DosesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2005Veronika Sa ABSTRACT The present study demonstrates the in vitro effect of hypericin-mediated PDT with fractionated light delivery. Cells were photosensitized with unequal light fractions separated by dark intervals (1 or 6 h). We compared the changes in viability, cell number, survival, apoptosis and cell cycle on HT-29 cells irradiated with a single light dose (12 J/cm2) to the fractionated light delivery (1 + 11 J/cm2) 24 and 48 h after photodynamic treatment. We found that a fractionated light regime with a longer dark period resulted in a decrease of hypericin cytotoxicity. Both cell number and survival were higher after light sensitization with a 6-h dark interval. DNA fragmentation occurred after a single light-dose application, but in contrast no apoptotic DNA formation was detected with a 6-h dark pause. After fractionation the percentage of cells in the G1 phase of the cell cycle was increased, while the proportion of cells in the G2 phase decreased as compared to a single light-dose application, i.e. both percentage of cells in the G1 and G2 phase of the cell cycle were near control levels. We presume that the longer dark interval after the irradiation of cells by first light dose makes them resistant to the effect of the second illumination. These findings confirm that the light application scheme together with other photodynamic protocol components is crucial for the photocytotoxicity of hypericin. [source] Evaluation of the Photosensitizer Tookad® for Photodynamic Therapy on the Syrian Golden Hamster Cheek Pouch Model: Light Dose, Drug Dose and Drug,light Interval Effects,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2003François Borle ABSTRACT We have evaluated the efficacy of the new photosensitizer (PS) Tookad® in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection,light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad® could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels. [source] Eradication of Multiple Myeloma and Breast Cancer Cells by TH9402-mediated Photodynamic Therapy: Implication for Clinical Ex Vivo Purging of Autologous Stem Cell Transplants,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2000N. Brasseur ABSTRACT High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1,2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5,10 ,M dye followed by a 90 min washout period and a light dose of 5,10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 × 106 cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. [source] Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCCPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2010Eleni Sotiriou We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions. [source] Photodynamic therapy for the treatment of a giant superficial basal cell carcinomaPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2009Donato Calista Summary A 74-year-old man was referred to our department for the treatment of a 15 × 15 cm superficial basal cell carcinoma (BCC) on his lumbar region. As surgical excision was considered too destructive, photodynamic therapy (PDT) was proposed. Methyl 5-aminolevulinate (MAL) cream was applied under occlusion for 3 h before illumination with a light-emitting diode lamp with an emission peak of 632 nm, a fluence rate of 83.3 mW/cm, and a light dose of 37 J/cm. A second MAL-PDT session was repeated 1 week later. The neoplastic area healed in 30 days. No recurrence has occurred after a 40-month follow-up period, but clinical observation continues. Although surgery still remains the treatment of choice for giant BCC, for which the local invasiveness and metastatic potential are well known, we offered our patient the option of PDT because we believed that classical surgery could hardly provide the same satisfactory outcome. As far as we know, this is the first case of giant BCC treated with PDT. [source] Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for psoriasis?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005Results of a randomized, observer-blinded study Summary Background, Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. Objectives, The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. Patients and methods, Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm,2, 10 J cm,2 or 20 J cm,2, respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3,4 days after the last irradiation. Results, Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm,2 resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm,2 and 5 J cm,2 decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm,2 and 10 J cm,2 or 5 J cm,2 was statistically significant (P = 0·003; P = 0·02), whereas no difference was found between 10 J cm,2 and 5 J cm,2 (P = 0·4). All patients reported some degree of PDT-induced stinging or burning during irradiation. Conclusions, The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis. [source] Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcomeBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2004M.B. Ericson Summary Background, Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives, The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods, Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580,650 nm) and fluence rates of 30 or 45 mW cm,2, and two groups with broad filter (580,690 nm) and fluence rates of 50 or 75 mW cm,2. The total cumulative light dose was 100 J cm,2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results, Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photobleaching dose (1/e) was found to be related to fluence rate, ranging from 4·5 ± 1·0 J cm,2 at 30 mW cm,2, to 7·3 ± 0·7 J cm,2 at 75 mW cm,2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm,2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm,2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm,2. Conclusions, Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm,2) seems preferable when performing PDT of AK using noncoherent light sources. [source] Photodynamic therapy of newly implanted glioma cells in the rat brainLASERS IN SURGERY AND MEDICINE, Issue 5 2006Steen J. Madsen PhD Abstract Background and Objective A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. Study Design/Materials and Methods Biodistribution studies on tumor-bearing animals were undertaken in order to determine the occurrence of photosensitizer in tumor cells invading normal brain. ALA,PDT toxicity in normal brain and gross tumor were evaluated from histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 hours after tumor cell implantation. Results Fluorescence microscopy of frozen tissue sections showed that photosensitizer content was limited and variable in tumor tissue invading normal brain. ALA,PDT with high light doses resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT. Conclusion The results show that ALA,PDT could not prevent tumors from forming if treatment was performed shortly after tumor initiation. This was likely due to inadequate levels of ALA/PpIX in the glioma cells. Lasers Surg. Med. © 2005 Wiley-Liss, Inc. [source] Unusual Photoinduced Response of mTHPC Liposomal Formulation (Foslip)PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2009Dzmitry Kachatkou Liposomal formulations of meso-tetra(hydroxyphenyl)chlorin (mTHPC) have already been proposed with the aim to optimize photodynamic therapy. Spectral modifications of these compounds upon irradiation have not yet been investigated. The objective of this study was to evaluate photobleaching properties of mTHPC encapsulated into dipalmitoylphosphatidylcholine (DPPC) liposomes, Foslip. Fluorescence measurements in DPPC liposomes with different DPPC:mTHPC ratios demonstrated a dramatic decrease in fluorescence anisotropy with increasing local mTHPC concentration, thus suggesting strong interactions between mTHPC molecules in lipid bulk medium. Exposure of Foslip suspensions to small light doses (<50 mJ/cm2) resulted in a substantial drop in fluorescence, which, however, was restored after addition to the sample of a non-ionic surfactant Triton X-100. We attributed this behavior to photoinduced fluorescence quenching. This effect depended strongly on the molar DPPC:mTHPC ratio and was revealed only for high local mTHPC concentrations. The results were interpreted supposing energy migration between closely located mTHPC molecules with its subsequent dissipation by the molecules of photoproduct acting as excitation energy traps. We further assessed the effect of photoinduced quenching in plasma protein solution. Relatively slow kinetics of photoinduced Foslip response during incubation in the presence of proteins was attributed to mTHPC redistribution from liposomal formulations to proteins. Therefore, changes in mTHPC distribution pattern in biological systems would be consistent with changes in photoinduced quenching and would provide valuable information on mTHPC interactions with a biological environment. [source] Synthesis, Photophysical Studies and Anticancer Activity of a New Halogenated Water-Soluble PorphyrinPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007Janusz M. D, browski ABSTRACT A water-soluble halogenated porphyrin, namely 5,10,15,20 -tetrakis(2-chloro-3-sulfophenyl)porphyrin (TCPPSO3H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO3H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO3H is non-toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time-dependent cellular uptake of TCPPSO3H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water-soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents. [source] Eradication of Multiple Myeloma and Breast Cancer Cells by TH9402-mediated Photodynamic Therapy: Implication for Clinical Ex Vivo Purging of Autologous Stem Cell Transplants,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2000N. Brasseur ABSTRACT High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1,2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5,10 ,M dye followed by a 90 min washout period and a light dose of 5,10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 × 106 cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. [source] Synovial ablation in a rabbit rheumatoid arthritis model using photodynamic therapyANZ JOURNAL OF SURGERY, Issue 7 2002Andrew D. Beischer Background: At present there is no ideal minimally invasive method for ablating inflamed synovium in joints that has been unresponsive to optimal medical management in patients with rheumatoid arthritis. The aim of this study was to determine whether photodynamic therapy could be used for this purpose. Methods: In a rabbit knee model of rheumatoid arthritis the pharmacokinetics of the photosensitizer Haematoporphyrin Derivative (HpD) into periarticular tissues and blood was measured following intravenous injection of HpD. The second phase of the study was to determine the histological effect of HpD activation by 63 nm light delivered via an intra-articular optic fibre using a dye pumped KTP-YAG laser. The light dose was varied from 0,200 joule/cm2. Results: Pharmacokinetic studies determined that inflamed synovium rapidly accumulated HpD, with peak levels being reached 12 h following intravenous injection. The ratio of HpD uptake into inflamed synovium versus peri-articular quadriceps muscle was found to be 22.8. Histological examination of the treated knees indicated that selective destruction of inflamed synovium was achieved at light doses 100 joules/cm2 and above. No significant effect was observed on normal intra-articular tissues. Conclusion: We have demonstrated that the first generation photosensitizer HpD selectively accumulates within inflamed synovium. Activation of HpD by intra-articular light administration resulted in selective ablation of the inflamed synovium. These findings indicate that PDT offers potential as a new selective, minimally invasive synovectomy technique. [source] Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for psoriasis?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005Results of a randomized, observer-blinded study Summary Background, Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. Objectives, The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. Patients and methods, Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm,2, 10 J cm,2 or 20 J cm,2, respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3,4 days after the last irradiation. Results, Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm,2 resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm,2 and 5 J cm,2 decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm,2 and 10 J cm,2 or 5 J cm,2 was statistically significant (P = 0·003; P = 0·02), whereas no difference was found between 10 J cm,2 and 5 J cm,2 (P = 0·4). All patients reported some degree of PDT-induced stinging or burning during irradiation. Conclusions, The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis. [source] | |||||||||||||