Effects of Fluence Rate on Cell Survival and Photobleaching in Meta-Tetra-(hydroxyphenyl)chlorin–photosensitized Colo 26 Multicell Tumor Spheroids¶

Coutier, Stéphanie; Mitra, Soumya; Bezdetnaya, Lina; Parache, R M; Georgakoudi, Irene; Foster, Thomas H.; Guillemin, François

doi:10.1562/0031-8655(2001)073<0297:eofroc>2.0.co;2

Cited by 74 publications

(71 citation statements)

References 26 publications

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“…Since the oxygen supply is one of the limiting factors in PDT, this phenomenon could result from a too high initial oxygen consumption imposed by a high irradiance. This hypothesis is in agreement with the data and calculations of Foster's group [31,32].…”

Section: Photobleaching Monitoring and Ros Reporter Systemsupporting

confidence: 91%

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

et al. 2006

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Background and Objectives: Photodynamic therapy (PDT) of superficial bladder cancer may cause damages to the normal surrounding bladder wall. Prevention of these is important for bladder healing. We studied the influence of photosensitizer concentration, irradiation parameters, and production of reactive oxygen species (ROS) on the photodynamically induced damage in the porcine urothelium in vitro. The aim was to determine the threshold conditions for the cell survival. Methods: Living porcine bladder mucosae were incubated with solution of hexylester of 5-aminolevulinic acid (HAL). The mucosae were irradiated with increasing doses and cell alterations were evaluated by scanning electron microscopy and by Sytox green fluorescence. The urothelial survival score was correlated with Protoporphyrin IX (PpIX) photobleaching and intracellular fluorescence of Rhodamine 123 reflecting the ROS production. Results: The mortality ratio was dependent on PpIX concentration. After 3 hours of incubation, the threshold radiant exposures for blue light were 0.15 and 0.75 J/cm 2 (irradiance 30 and 75 mW/cm 2 , respectively) and for white light 0.55 J/cm 2 (irradiance 30 mW/cm 2 ). Photobleaching rate increased with decreasing irradiance. Interestingly, the DHR123/R123 reporter system correlated well with the threshold exposures under all conditions used. Conclusions: We have determined radiant exposures sparing half of normal urothelial cells. We propose that the use of low irradiance combined with systems reporting the ROS production in the irradiated tissue could improve the in vivo dosimetry and optimize the PDT. Lasers Surg.

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Section: Photobleaching Monitoring and Ros Reporter Systemsupporting

confidence: 91%

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

et al. 2006

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“…They showed that, for a given total light°uence, both the 1 O 2 counts and the tumor response decreased as the°uence rate increased (from 30 to 120 mWcm À1 using an interstitial diffusing¯ber to deliver the light). This reduction in PDT e±cacy at high light°uence rates has been reported also in vitro 19 and in vivo 20 and is well understood in terms of photochemical depletion of ground-state molecular oxygen. 21 A particular advantage of the luminescence instrument used by Yamamoto et al 13 was the ability to collect the luminescence emitted from the tumor by a¯ber optic bundle.…”

Section: Discussionsupporting

confidence: 69%

Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

Wilson

Patterson

et al. 2015

J. Innov. Opt. Health Sci.

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Excited-state singlet oxygen ( 1 O 2 ), generated during photodynamic therapy (PDT), is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR) luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC) in an animal model comprising luciferase-and green°uorescent protein (GFP)-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classi¯ed in individual tumors as \non", \moderate" and \strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1 O 2 counts demonstrated clear correlation, indicating that 1 O 2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

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“…Previous studies from our group have demonstrated that BPD-PDT significantly decreases the size of 3-D OvCa nodules 20 and synergistically enhances carboplatin efficacy. 21 These and other studies 31,59,61,68 suggest a role for 3-D models in improved treatment planning, including for PDT regimens. The myriad of variables that influence PDT outcomes, including the marginal benefit gained from dose escalation, PS concentration, fluence, and the metrics used to evaluate treatment response require further optimization.…”

Section: Introductionmentioning

confidence: 85%

Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer

Anbil¹,

Rizvi²,

Alagic³

et al. 2013

J. Biomed. Opt

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Abstract. Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching and viability, suggesting that it was a better reporter of PDT efficacy than total volume, which did not correlate with either metric. Based on these findings, live volume and viability are used to probe the susceptibilities of tumor populations to a range of PDT dose parameters administered using 0.25, 1, and 10 μM benzoporphyrin derivative (BPD). PDT with 0.25 μM BPD produces the most significant reduction in live volume and viability and mediates a substantial shift toward small nodules. Increasingly sophisticated bioengineered models may complement current treatment planning approaches and provide unique opportunities to critically evaluate key parameters including metrics of therapeutic response.

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Effects of Fluence Rate on Cell Survival and Photobleaching in Meta-Tetra-(hydroxyphenyl)chlorin–photosensitized Colo 26 Multicell Tumor Spheroids¶

Cited by 74 publications

References 26 publications

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

Hexyl‐aminolevulinate‐mediated photodynamic therapy: How to spare normal urothelium. An in vitro approach

Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer

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