Topical photodynamic therapy at low fluence rates – theory and practice

Langmack, K A; Mehta, R K; Twyman, Paul; Norris, P.G.

doi:10.1016/s1011-1344(01)00116-6

Cited by 65 publications

(65 citation statements)

References 26 publications

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“…Both of these effects will contribute to tumor destruction. Some clinical and experimental data have been reported recently pointing to a significant tumor cure effect [12,19]. From the result of our cellkilling experiment, we can conclude that lower fluence rate treatments may be more effective in increasing the killing rate of tumor cells, which directly indicates better local tumor control.…”

Section: Discussionsupporting

confidence: 58%

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Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy

2005

Lasers Med Sci

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During the process of photodynamic therapy (PDT), problems arise such as stasis or occlusion of microvasculature, tumor oxygen depletion, and photosensitizer bleaching. This study shows that the first problem could be reduced by using a lower fluence rate light source in PDT. Microvasculature damage was studied experimentally in hematoporphyrin derivativemediated PDT against light fluence rate, and, to some extent, less microvasculature damage was induced under 75 mW/cm 2 illumination than under 150 mW/cm 2 . Histology of vessels at the end of PDT showed that vessel damage could be observed in both groups, indicating that the microvasculature would eventually be damaged as long as the administration of light fluence was sufficient and regardless of the illuminating fluence rates. Thus microvasculature damage induced by low fluence rate illumination could also be effective in tumor control after PDT. The cell-killing experiment was performed in vitro and designed so that cell-killing rate was influenced only by light characteristics. The higher cellkilling rate caused by 75 mW/cm 2 illumination indicated that lower fluence rate light could enhance the light absorbency or decrease the bleaching of photosensitizer.

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Section: Discussionsupporting

confidence: 58%

“…Cell-killing models of PDT related to the light dose have been introduced to show the relationship between the fluence rate and the 50% killing dose of PDT [12]. Some experiments concerning the microscopic cell-killing rate at different fluence rates are suggested for further research.…”

Section: Introductionmentioning

confidence: 99%

Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy

2005

Lasers Med Sci

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“…In BCCs, photodynamic efficiency (loss of light absorbance as photosenstizer is used in the photodynamic process) decreased with increased fluence rate; 20 mW cm À2 of narrowband red light was most efficient (Cottrell et al, 2008). A 635 nm red light source was as effective in the treatment of superficial BCCs at 12.6 J cm À2 , delivered at 7 mW cm À2 over 30 minutes, as standard treatment (37 J cm À2 over 8 minutes; i.e., 75 mW cm À2 ; Langmack et al, 2001). There is a suggestion that low-irradiance ambulatory ALA-PDT (12 mW cm À2 ) may also be effective (Moseley et al, 2006).…”

Section: Discussionmentioning

confidence: 98%

“…Murine studies have shown that lower-fluence rates cause more efficient photobleaching and greater tissue damage by topical ALA-PDT (Robinson et al, 1998), and yield better tumor kill after systemic PDT (Sitnik and Henderson, 1998;Iinuma et al, 1999). Preliminary human studies also suggest that ALA/MAL-PDT with lower-fluence rates may be as or more effective than current protocols (Langmack et al, 2001;Ericson et al, 2004;Cottrell et al, 2008). PDT is highly immunosuppressive in mice (Elmets and Bowen, 1986), with suggestion that this may be prevented or even reversed by lowering fluence rates (Sitnik and Henderson, 1998;Henderson et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Frost

Halliday

Damian

2011

Journal of Investigative Dermatology

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Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes.

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“…In this sense the work here presented complements others already published. 1,4,5,[28][29][30][31] A model taking into account the main effects occurring during PDT applications allows us to understand the main facts for fluences lower than 250 J / cm 2 . Differences observed for higher fluences can be qualitatively explained based on a hypothesis of the establishment of a balance between photon absorption by the PS and the rate of molecular oxygen depletion.…”

Section: Discussionmentioning

confidence: 99%

Possibility for a full optical determination of photodynamic therapy outcome

Vollet‐Filho¹,

Menezes²,

Moriyama³

et al. 2009

Journal of Applied Physics

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The microfluidic system for studies of carcinoma and normal cells interactions after photodynamic therapy (PDT) procedures Biomicrofluidics 5, 041101 (2011) Drug injection into fat tissue with a laser based microjet injector J. Appl. Phys. 109, 093105 (2011) A near infrared instrument to monitor relative hemoglobin concentrations of human bone tissue in vitro and in vivo Rev. Sci. Instrum. 81, 043111 (2010) Mechanism of oxidative stress generation in cells by localized near-infrared femtosecond laser excitation Appl. Phys. Lett. 95, 233702 (2009) Probing nanoantenna-directed photothermal destruction of tumors using noninvasive laser irradiation Appl. Phys. Lett. 95, 233701 (2009) Additional information on J. Appl. Phys. The efficacy of photodynamic therapy ͑PDT͒ depends on a variety of parameters: concentration of the photosensitizer at the time of treatment, light wavelength, fluence, fluence rate, availability of oxygen within the illuminated volume, and light distribution in the tissue. Dosimetry in PDT requires the congregation of adequate amounts of light, drug, and tissue oxygen. The adequate dosimetry should be able to predict the extension of the tissue damage. Photosensitizer photobleaching rate depends on the availability of molecular oxygen in the tissue. Based on photosensitizers photobleaching models, high photobleaching has to be associated with high production of singlet oxygen and therefore with higher photodynamic action, resulting in a greater depth of necrosis. The purpose of this work is to show a possible correlation between depth of necrosis and the in vivo photosensitizer ͑in this case, Photogem®͒ photodegradation during PDT. Such correlation allows possibilities for the development of a real time evaluation of the photodynamic action during PDT application. Experiments were performed in a range of fluence ͑0 -450 J / cm 2 ͒ at a constant fluence rate of 250 mW/ cm 2 and applying different illumination times ͑0-1800 s͒ to achieve the desired fluence. A quantity was defined ͑ ͒ as the product of fluorescence ratio ͑related to the photosensitizer degradation at the surface͒ and the observed depth of necrosis. The correlation between depth of necrosis and surface fluorescence signal is expressed in and could allow, in principle, a noninvasive monitoring of PDT effects during treatment. High degree of correlation is observed and a simple mathematical model to justify the results is presented.

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Topical photodynamic therapy at low fluence rates – theory and practice

Cited by 65 publications

References 26 publications

Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy

Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Possibility for a full optical determination of photodynamic therapy outcome

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