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Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid.

Niedre MJ, Yu CS, Patterson MS, Wilson BC - Br. J. Cancer (2005)

Bottom Line: Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the (1)O(2) luminescence in cell suspensions over a wide range of treatment parameters.The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm(-2) of pulsed 523 nm light at 50 mW cm(-2), or to 50 J cm(-2) at 15 or 150 mW cm(-2). (1)O(2) luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment.However, in all cases the responses increased with the (1)O(2) luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between (1)O(2) generation and photobiological response.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biophysics, Ontario Cancer Institute/University Health Network Ontario, Canada.

ABSTRACT
Although singlet oxygen ((1)O(2)) has long been proposed as the primary reactive oxygen species in photodynamic therapy (PDT), it has only recently been possible to detect it in biological systems by its luminescence at 1270 nm. Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the (1)O(2) luminescence in cell suspensions over a wide range of treatment parameters. Here, we extend this to test the hypothesis that the photobiological response in vivo is also correlated with (1)O(2) generation, independent of individual treatment parameters. The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm(-2) of pulsed 523 nm light at 50 mW cm(-2), or to 50 J cm(-2) at 15 or 150 mW cm(-2). (1)O(2) luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment. As observed by other authors, a strong irradiance dependence of the PDT effect was observed. However, in all cases the responses increased with the (1)O(2) luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between (1)O(2) generation and photobiological response.

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Typical NIR spectra measured from single sensitised, unsensitised and hypoxic animals. For the sensitised animal, the individual spectra were measured at different times during treatment. For the control and hypoxic animals, error bars reflect the standard deviation of four spectra acquired for the same animal.
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fig2: Typical NIR spectra measured from single sensitised, unsensitised and hypoxic animals. For the sensitised animal, the individual spectra were measured at different times during treatment. For the control and hypoxic animals, error bars reflect the standard deviation of four spectra acquired for the same animal.

Mentions: Figure 2 shows typical, 5-wavelength spectra measured in the pilot group, including the sensitised, unsensitised and euthanised animals (50 mW cm−2). As expected for 1O2 luminescence, a clear 1270 nm peak was observed for the live sensitised animals. As will be demonstrated below, significant variability was observed both in terms of 1O2 generation and treatment response, even between animals receiving PDT under the same conditions. For this reason, representative data from a single sensitised animal are shown, as opposed to the average of the 1O2 luminescence observed from all of the live sensitised animals. A small but still significant peak at 1270 nm was observed in the unsensitised control animals, most likely due to 1O2 generated from naturally occurring porphyrins in the skin. No peak was observed at 1270 nm in the sensitised but euthanised animals, confirming the oxygen dependence of the signal. Hence, the system was capable of measuring 1O2 luminescence in this in vivo model.


Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid.

Niedre MJ, Yu CS, Patterson MS, Wilson BC - Br. J. Cancer (2005)

Typical NIR spectra measured from single sensitised, unsensitised and hypoxic animals. For the sensitised animal, the individual spectra were measured at different times during treatment. For the control and hypoxic animals, error bars reflect the standard deviation of four spectra acquired for the same animal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361839&req=5

fig2: Typical NIR spectra measured from single sensitised, unsensitised and hypoxic animals. For the sensitised animal, the individual spectra were measured at different times during treatment. For the control and hypoxic animals, error bars reflect the standard deviation of four spectra acquired for the same animal.
Mentions: Figure 2 shows typical, 5-wavelength spectra measured in the pilot group, including the sensitised, unsensitised and euthanised animals (50 mW cm−2). As expected for 1O2 luminescence, a clear 1270 nm peak was observed for the live sensitised animals. As will be demonstrated below, significant variability was observed both in terms of 1O2 generation and treatment response, even between animals receiving PDT under the same conditions. For this reason, representative data from a single sensitised animal are shown, as opposed to the average of the 1O2 luminescence observed from all of the live sensitised animals. A small but still significant peak at 1270 nm was observed in the unsensitised control animals, most likely due to 1O2 generated from naturally occurring porphyrins in the skin. No peak was observed at 1270 nm in the sensitised but euthanised animals, confirming the oxygen dependence of the signal. Hence, the system was capable of measuring 1O2 luminescence in this in vivo model.

Bottom Line: Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the (1)O(2) luminescence in cell suspensions over a wide range of treatment parameters.The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm(-2) of pulsed 523 nm light at 50 mW cm(-2), or to 50 J cm(-2) at 15 or 150 mW cm(-2). (1)O(2) luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment.However, in all cases the responses increased with the (1)O(2) luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between (1)O(2) generation and photobiological response.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biophysics, Ontario Cancer Institute/University Health Network Ontario, Canada.

ABSTRACT
Although singlet oxygen ((1)O(2)) has long been proposed as the primary reactive oxygen species in photodynamic therapy (PDT), it has only recently been possible to detect it in biological systems by its luminescence at 1270 nm. Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the (1)O(2) luminescence in cell suspensions over a wide range of treatment parameters. Here, we extend this to test the hypothesis that the photobiological response in vivo is also correlated with (1)O(2) generation, independent of individual treatment parameters. The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm(-2) of pulsed 523 nm light at 50 mW cm(-2), or to 50 J cm(-2) at 15 or 150 mW cm(-2). (1)O(2) luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment. As observed by other authors, a strong irradiance dependence of the PDT effect was observed. However, in all cases the responses increased with the (1)O(2) luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between (1)O(2) generation and photobiological response.

Show MeSH
Related in: MedlinePlus