Effect of Light Fluence Rate on Mammalian Cells Photosensitization by Chloroaluminium Phthalocyanine Tetrasulphonate

Ben‐Hur, E.; Kol, R.; Riklis, E.; Marko, R.; Rosenthal, I.

doi:10.1080/09553008714550951

Cited by 25 publications

(10 citation statements)

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“…Many workers report an initial shoulder region on curves of cell survival vs. light dose, obtained in vitro. This has been found in experiments using benign cell lines, e.g., Chinese hamster ovary cells (Gomer & Smith, 1980) and human lymphocytes (Ben Hur et al, 1987) and for cells derived from malignancies, e.g., NHIK cells from carcinoma in situ of the cervix (Moan et al, 1979a) and mouse mammary carcinoma cells (Dougherty et al, 1976). It has also been reported in experiments using different photosensitising drugs, e.g., haematoporphyrin (HP; Moan et al, 1979b), haematoporphyrin derivative (HPD; Christensen et al, 1984), meso-tetra sulphophenyl porphine (TPPS; Evensen et al, 1987) and chloroaluminium phthalocyanine (Ben Hur et al, 1985).…”

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confidence: 93%

The effect of fractionation of light treatment on necrosis and vascular function of normal skin following photodynamic therapy

Benstead

Moore²

1988

Br J Cancer

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Summary Sparing of normal tissue, mouse tail skin, by fractionation of light treatment in photodynamic therapy has been demonstrated in BDF1 mice injected with 2mg tetrasodium-meso-tetra(4-sulphophenyl) porphine dodecahydrate i.v. When the time between 2 fractions of 67.5 Jcm-2 and 90Jcm-2 was increased to 2 and 4 days respectively the incidence of necrosis fell to that expected after a single fraction. Blood flow in the tail skin 5 days after the second light fraction, as measured by the clearance of an intradermally injected solution of 133xenon in 0.9% saline, returned to control values when the time between 2 fractions was 2 days with 67.51Jcm-2 fractions, and 3 days with 90Jcm-2 fractions. al., 1987) and chloroaluminium phthalocyanine (Ben Hur et al., 1985).Evidence that environmental conditions may modulate the expression of this sublethal damage initially came from studies on the effect of temperature on the shapes of cell survival curves following PDT. Moan et al. (1979a) noted that following exposure to HP, irradiation of NHIK cells in vitro at 4°C resulted in more efficient inactivation than irradiation at 37°C and there was no shoulder on the cell survival curve. Subsequently, Gomer et al. (1985) demonstrated an inhibition of repair of 'potentially lethal damage' when Chinese hamster lung fibroblasts that had received prolonged exposure to HPD, were held post-irradiation at 4°C or in the presence of the metabolic inhibitor caffeine.Attempts to measure repair of sub-lethal damage by splitdose experiments in vitro have been reported by Moan et al. (1979a), who found that for NHIK cells exposed to light in the presence of HP, a given total light dose was more efficient when it was fractionated than when given in a single exposure. Subsequently however, Christensen et al. (1985) used the same cell line to demonstrate that relative survival after two doses was a complex function of the interval between doses and that 'sparing' occurred with a 3 h interval. Bellnier & Lin (1985) found that survival of EJ human urinary bladder carcinoma cells rapidly increased with interval between two light fractions, reaching a maximum at 9 h.The aim of the present study was to determine whether or not fractionation of light treatment resulted in sparing of tissue in vivo, using as a model normal mouse tail skin. (Sacchini et al., 1987). Tissue injury was assessed using two endpoints:1. the incidence of tail necrosis, as described by Moore et al. (1986); and 2. blood flow in the mouse tail skin 5 days after a second light fraction as measured by the clearance of 133xenon injected intradermally. There is evidence that impairment of vascular function is an important mechanism resulting in damage to both malignant and normal tissues. A previous study found an initial impairment in blood flow following PDT but this returned to normal by day 5 at low light doses. However, at light doses greater than the threshold for skin necrosis, there was increasing impairment of blood flow on day 5 (Benstead & Moore, 1988). Material...

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confidence: 93%

The effect of fractionation of light treatment on necrosis and vascular function of normal skin following photodynamic therapy

Benstead

Moore²

1988

Br J Cancer

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“…A number of in vitro [14–17] and in vivo [18–22] studies suggest that the threshold light fluence necessary for efficient elimination of tumor cells depends on the rate at which the fluence is delivered. To date, most clinical PDT trials have employed short-term high fluence rate intraoperative or stereotactic light delivery techniques [23,24].…”

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confidence: 99%

The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids

et al. 2009

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Background and Objective Achieving local control of gliomas with photodynamic therapy (PDT) requires the delivery of adequate light fluences to depths of 1–2 cm in the resection margin where the majority of local recurrences originate. This is clinically impractical with current single-shot, intraoperative PDT treatments due to the length of time required to deliver adequate fluences. Multiple or extended treatment protocols would therefore seem to be required. The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated PDT using single or, repetitive light delivery protocols was investigated at both low and ultra low fluence rates. Study Design/Materials and Methods Human glioma spheroids (400 μm diameter) were subjected to sub-threshold light fluence (1.5, 3, or 6 J cm−2) ALA–PDT consisting of four light delivery schemes: single treatment given over either 1 or 24 hours, repetitive treatment given either as four 1 hour light treatments separated by a 4 day interval, or 24 hours light delivery, consisting of four 24 hours treatments separated by a 3 day interval. Treatment efficacy was evaluated using a growth assay. In some cases, confocal microscopy was used to image cell viability. Results The repetitive and single light treatment protocols were most effective when delivered at ultra low (μW cm−2) fluence rates. In all cases, growth inhibition was light dose-dependent. The repetitive ultra low fluence rate treatment (1.5 J cm−2; irradiance = 17 μW cm−2) light delivery protocol was the most effective resulting in total growth inhibition during the 2-week observation period. Conclusion Ultra low light fluence rate ALA–PDT results in significant spheroid growth inhibition. Repeated administration of ALA was required during repetitive and/or protracted single PDT treatment protocols. The existence of a lower fluence rate limit, below which the efficacy of threshold light fluences diminish was not found in these studies.

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“…However, due to the high attenuation of light in the brain tissue (23), long treatment times are required in order to deliver sufficient light doses (fluences) to depths of 1-2 cm in the resection cavity. Furthermore, a number of in vitro (24,25) and in vivo (26)(27)(28)(29) studies suggest that response to PDT depends not only on total fluence, but also on the rate at which the fluence is delivered-lower fluence rates appear more efficacious in many instances. Although fluence rate effects have been observed in numerous systems, a systematic study of such effects in a human glioma spheroid model using ALA has not been attempted.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy of Human Glioma Spheroids Using 5-Aminolevulinic Acid¶

Madsen¹,

Sun²,

Tromberg³

et al. 2000

Photochem Photobiol

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The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily convert ALA to protoporphyrin IX throughout the entire spheroid volume. The central finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rate at which the fluence is delivered. At low fluences (< or = 50 J cm-2), lower fluence rates are more effective. At a fluence of 50 J cm-2, near-total spheroid kill is observed at fluence rates of as low as 10 mW cm-2. The fluence rate effect is not as pronounced at higher fluences (> 50 J cm-2), where a favorable response is observed throughout the range of fluence rates investigated. The clinical implications of these findings are discussed.

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Effect of Light Fluence Rate on Mammalian Cells Photosensitization by Chloroaluminium Phthalocyanine Tetrasulphonate

Cited by 25 publications

References 12 publications

The effect of fractionation of light treatment on necrosis and vascular function of normal skin following photodynamic therapy

The effect of fractionation of light treatment on necrosis and vascular function of normal skin following photodynamic therapy

The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids

Photodynamic Therapy of Human Glioma Spheroids Using 5-Aminolevulinic Acid¶

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