In vivo TUMOR OXYGEN TENSION MEASUREMENTS FOR THE EVALUATION OF THE EFFICIENCY OF PHOTODYNAMIC THERAPY

Tromberg, Bruce J.; Orenstein, Arie; Kimel, S.; Barker, Steven J.; Hyatt, John A.; Nelson, J. Stuart; Berns, Michael W.

doi:10.1111/j.1751-1097.1990.tb04193.x

Cited by 199 publications

(112 citation statements)

References 18 publications

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“…This study confirms the concept of photochemical oxygen depletion during PDT, which was put forward by Tromberg et al (1990) and Foster et al (1991), and provides direct experimental evidence of PDT-induced oxygenation changes in a preclinical tumour system.…”

Section: Discussionsupporting

confidence: 87%

“…This observation is consistent with the concept of photochemical oxygen depletion and observations by Tromberg et al (1990), and does not agree with the finding by Fingar et al (1992b) of PDTinduced vascular constriction lasting for -1 h after treatment. (3) The observed recovery of tumour pO2 at low fluence rate with low-treatment fluence may be due to a decrease in metabolic oxygen consumption as a result of direct cell effects during PDT (Gibson et al, 1990), i.e.…”

Section: Discussioncontrasting

confidence: 65%

“…Hypoxia may result from PDT-mediated damage to the microvasculature, which usually develops with time after PDT, but which can occur acutely during light delivery at high photosensitizer and light doses with certain photosensitizers (Henderson hypoxia is the consumption of 3°2 in the PDT-mediated formation and consumption of 102. Very rapid and substantial reductions in tissue oxygen tensions upon illumination of photosensitized tissue have been detected with transcutaneous oxygen electrodes by Tromberg et al (1990). Mathematical modelling by Foster et al (1991) has demonstrated that the rate of oxygen consumption during Photofrin PDT may be significant enough to move a fraction of the tumour into very low levels of oxygenation, outpacing the rate of oxygen diffusion from the capillaries and shrinking the radius of oxygenated tissue volume around them.…”

mentioning

confidence: 99%

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Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Sitnik

Hampton²,

Henderson³

1998

Br J Cancer

248

204

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Summary It has been proposed that the generation of 102 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on P02, in the murine RIF tumour during and after PDT using 5 mg kg-' Photofrin and fluence rates of 30, 75 or 150 mW cm-2. Median P02 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour P02 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm-2) P02 recovered at the 30 mW cm-2 fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm-2 fluence rate (median P02 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm-2 median tumour P02 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm-2 at 30 mW cm-2 caused significantly (P= 0.0004) longer median tumour regrowth times than PDT at 150 mW cm-2, indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour P02, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.

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Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 65%

mentioning

confidence: 99%

See 1 more Smart Citation

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Sitnik

Hampton²,

Henderson³

1998

Br J Cancer

248

204

View full text Add to dashboard Cite

show abstract

“…16 Tromberg et al 17 observed that during PDT using high fluence rate, oxygen depletion occurs with temperature increase. Following their conclusions, if the hyperthermia effect is high enough to contribute to the therapeutic process, the induction of the synergistic effect may have taken place, enhancing tissue damage during PDT.…”

Section: Resultsmentioning

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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“…Other studies have also concluded lower fluence rate treatments can preserve the status of oxygen for a more effective PDT [6,9,17,18], and it has been recognized that light fluence rates play a major role in the tumor oxygenation status during PDT exposure. Our work explains the mechanism of oxygen preservation under low fluence illumination in PDT to some extent.…”

Section: Discussionmentioning

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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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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In vivo TUMOR OXYGEN TENSION MEASUREMENTS FOR THE EVALUATION OF THE EFFICIENCY OF PHOTODYNAMIC THERAPY

Cited by 199 publications

References 18 publications

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Possibility for a full optical determination of photodynamic therapy outcome

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

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