Abstract

The effectiveness of photodynamic therapy is strongly dependent on the availabilty of oxygen. In the present paper we show that the ratio between photosensitiser phosphorescence and fluorescence is a parameter that can be used to monitor the competition between singlet oxygen production and other processes quenching the photosensitiser triplet state. We present a theoretical basis for the validity of this approach and a series of in vitro imaging experiments.

©2004 Optical Society of America

Full Article  |  PDF Article
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References

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  1. W.M. Star, “Light dosimetry in vivo,” Phys. Med. Biol. 42, 763–87 (1997).
    [Crossref] [PubMed]
  2. B.C. Wilson, M.S. Patterson, and L. Lilge “Implicit and Explicit Dosimetry in Photodynamic Therapy: A New Paradigm,” Lasers Med. Sci. 12, 182–99 (1997)
    [Crossref] [PubMed]
  3. D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
    [Crossref] [PubMed]
  4. D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
    [Crossref]
  5. I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
    [Crossref] [PubMed]
  6. J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
    [Crossref] [PubMed]
  7. J.C. Finlay, S. Mitra, and T.H. Foster. “In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features,” Photochem. Photobiol. 75, 282–8 (2002)
    [Crossref] [PubMed]
  8. L. Kunz and A.J. MacRobert. “Intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl) chlorin exhibits a complex dependence on oxygen level and fluence rate,” Photochem. Photobiol. 75, 28–35 (2002)
    [Crossref] [PubMed]
  9. V.X. Yang, P.J. Muller, P. Herman, and B.C. Wilson. “A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative“ Photofrin-photodynamic therapy of brain tumors. Lasers Surg. Med. 32,: 224–32 (2003)
  10. H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
    [Crossref] [PubMed]
  11. J.G. Parker. “Optical monitoring of singlet oxygen during photodynamic treatment of tumors,” IEEE Circ. Devices Mag.10–21. (1987)
    [Crossref]
  12. M.S. Patterson, S.J. Madsen, and B.C. Wilson. “Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy,” J. Photochem. Photobiol. B. 5, 69–84 (1990)
    [Crossref] [PubMed]
  13. M.J. Niedre, M.S. Patterson, and B.C. Wilson. “Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo,” Photochem. Photobiol. 75: 382–91 (2002)
    [Crossref] [PubMed]
  14. B.W. Pogue, T. Momma, H.C. Wu, and T. Hasan “Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light,” Br. J. Cancer 80, 344–351 (1999)
    [Crossref] [PubMed]
  15. H.J.C.M. Sterenborg, M. Janson, and M.J.C. van Gemert. “A novel frequency domain technique for measurement of triplet decay times using two diode lasers,” Phys.Med. Biol. 44, 1419–1426 (1999)
    [Crossref] [PubMed]
  16. M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
    [PubMed]
  17. S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
    [Crossref] [PubMed]
  18. H.J.C.M. Sterenborg and M.J.C. van Gemert. “Photodynamic therapy with pulsed sources; a theoretical analysis,” Phys. Med. Biol. 41, 835–50 (1994)
    [Crossref]
  19. T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
    [Crossref] [PubMed]

2003 (4)

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

V.X. Yang, P.J. Muller, P. Herman, and B.C. Wilson. “A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative“ Photofrin-photodynamic therapy of brain tumors. Lasers Surg. Med. 32,: 224–32 (2003)

M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
[PubMed]

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

2002 (5)

H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

M.J. Niedre, M.S. Patterson, and B.C. Wilson. “Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo,” Photochem. Photobiol. 75: 382–91 (2002)
[Crossref] [PubMed]

J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
[Crossref] [PubMed]

J.C. Finlay, S. Mitra, and T.H. Foster. “In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features,” Photochem. Photobiol. 75, 282–8 (2002)
[Crossref] [PubMed]

L. Kunz and A.J. MacRobert. “Intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl) chlorin exhibits a complex dependence on oxygen level and fluence rate,” Photochem. Photobiol. 75, 28–35 (2002)
[Crossref] [PubMed]

2000 (1)

D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
[Crossref]

1999 (2)

B.W. Pogue, T. Momma, H.C. Wu, and T. Hasan “Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light,” Br. J. Cancer 80, 344–351 (1999)
[Crossref] [PubMed]

H.J.C.M. Sterenborg, M. Janson, and M.J.C. van Gemert. “A novel frequency domain technique for measurement of triplet decay times using two diode lasers,” Phys.Med. Biol. 44, 1419–1426 (1999)
[Crossref] [PubMed]

1998 (1)

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
[Crossref] [PubMed]

1997 (2)

W.M. Star, “Light dosimetry in vivo,” Phys. Med. Biol. 42, 763–87 (1997).
[Crossref] [PubMed]

B.C. Wilson, M.S. Patterson, and L. Lilge “Implicit and Explicit Dosimetry in Photodynamic Therapy: A New Paradigm,” Lasers Med. Sci. 12, 182–99 (1997)
[Crossref] [PubMed]

1994 (1)

H.J.C.M. Sterenborg and M.J.C. van Gemert. “Photodynamic therapy with pulsed sources; a theoretical analysis,” Phys. Med. Biol. 41, 835–50 (1994)
[Crossref]

1991 (1)

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

1990 (1)

M.S. Patterson, S.J. Madsen, and B.C. Wilson. “Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy,” J. Photochem. Photobiol. B. 5, 69–84 (1990)
[Crossref] [PubMed]

1987 (1)

J.G. Parker. “Optical monitoring of singlet oxygen during photodynamic treatment of tumors,” IEEE Circ. Devices Mag.10–21. (1987)
[Crossref]

Boere, I.A.

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

Brown, S.B.

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
[Crossref] [PubMed]

Bryant, R.G.

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

de Bruijn, H.S.

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
[Crossref]

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
[Crossref] [PubMed]

de Bruin, R.W.

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

de Wolf, W.J.

D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
[Crossref]

Dysart, J.S.

J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
[Crossref] [PubMed]

Farrell, T.J.

J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
[Crossref] [PubMed]

Finlay, J.C.

J.C. Finlay, S. Mitra, and T.H. Foster. “In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features,” Photochem. Photobiol. 75, 282–8 (2002)
[Crossref] [PubMed]

Foster, T.H.

J.C. Finlay, S. Mitra, and T.H. Foster. “In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features,” Photochem. Photobiol. 75, 282–8 (2002)
[Crossref] [PubMed]

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

Gibson, S.L.

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

Gilead, A.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

Gross, S.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

Hasan, T.

B.W. Pogue, T. Momma, H.C. Wu, and T. Hasan “Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light,” Br. J. Cancer 80, 344–351 (1999)
[Crossref] [PubMed]

Herman, P.

V.X. Yang, P.J. Muller, P. Herman, and B.C. Wilson. “A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative“ Photofrin-photodynamic therapy of brain tumors. Lasers Surg. Med. 32,: 224–32 (2003)

Hilf, R.

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

Janson, M.

H.J.C.M. Sterenborg, M. Janson, and M.J.C. van Gemert. “A novel frequency domain technique for measurement of triplet decay times using two diode lasers,” Phys.Med. Biol. 44, 1419–1426 (1999)
[Crossref] [PubMed]

Knox, R.S.

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

Korbelik, M.

H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

Kunz, L.

L. Kunz and A.J. MacRobert. “Intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl) chlorin exhibits a complex dependence on oxygen level and fluence rate,” Photochem. Photobiol. 75, 28–35 (2002)
[Crossref] [PubMed]

Lilge, L.

B.C. Wilson, M.S. Patterson, and L. Lilge “Implicit and Explicit Dosimetry in Photodynamic Therapy: A New Paradigm,” Lasers Med. Sci. 12, 182–99 (1997)
[Crossref] [PubMed]

Lui, H.

H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

MacAulay, C.

H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

MacRobert, A.J.

L. Kunz and A.J. MacRobert. “Intracellular photobleaching of 5,10,15,20-tetrakis(m-hydroxyphenyl) chlorin exhibits a complex dependence on oxygen level and fluence rate,” Photochem. Photobiol. 75, 28–35 (2002)
[Crossref] [PubMed]

Madsen, S.J.

M.S. Patterson, S.J. Madsen, and B.C. Wilson. “Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy,” J. Photochem. Photobiol. B. 5, 69–84 (1990)
[Crossref] [PubMed]

McLean, D.I.

H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

Mitra, S.

J.C. Finlay, S. Mitra, and T.H. Foster. “In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance-dependent features,” Photochem. Photobiol. 75, 282–8 (2002)
[Crossref] [PubMed]

Momma, T.

B.W. Pogue, T. Momma, H.C. Wu, and T. Hasan “Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light,” Br. J. Cancer 80, 344–351 (1999)
[Crossref] [PubMed]

Muller, P.J.

V.X. Yang, P.J. Muller, P. Herman, and B.C. Wilson. “A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative“ Photofrin-photodynamic therapy of brain tumors. Lasers Surg. Med. 32,: 224–32 (2003)

Murant, R.S.

T.H. Foster, R.S. Murant, R.G. Bryant, R.S. Knox, S.L. Gibson, and R. Hilf. “Oxygen consumption and diffusion effects in photodynamic therapy,” Radiat. Res. 126, 296–303 (1991)
[Crossref] [PubMed]

Neeman, M.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

Niedre, M.J.

M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
[PubMed]

M.J. Niedre, M.S. Patterson, and B.C. Wilson. “Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo,” Photochem. Photobiol. 75: 382–91 (2002)
[Crossref] [PubMed]

Parker, J.G.

J.G. Parker. “Optical monitoring of singlet oxygen during photodynamic treatment of tumors,” IEEE Circ. Devices Mag.10–21. (1987)
[Crossref]

Patterson, M.S.

M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
[PubMed]

M.J. Niedre, M.S. Patterson, and B.C. Wilson. “Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo,” Photochem. Photobiol. 75: 382–91 (2002)
[Crossref] [PubMed]

J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
[Crossref] [PubMed]

B.C. Wilson, M.S. Patterson, and L. Lilge “Implicit and Explicit Dosimetry in Photodynamic Therapy: A New Paradigm,” Lasers Med. Sci. 12, 182–99 (1997)
[Crossref] [PubMed]

M.S. Patterson, S.J. Madsen, and B.C. Wilson. “Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy,” J. Photochem. Photobiol. B. 5, 69–84 (1990)
[Crossref] [PubMed]

Pogue, B.W.

B.W. Pogue, T. Momma, H.C. Wu, and T. Hasan “Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light,” Br. J. Cancer 80, 344–351 (1999)
[Crossref] [PubMed]

Robinson, D.J.

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
[Crossref]

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
[Crossref] [PubMed]

Salomon, Y.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

Scherz, A.

S. Gross, A. Gilead, A. Scherz, M. Neeman, and Y. Salomon. “Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI,” Nat. Med. 9, 1327–31 (2003)
[Crossref] [PubMed]

Secord, A.J.

M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
[PubMed]

Singh, G.

J.S. Dysart, M.S. Patterson, T.J. Farrell, and G. Singh. “Relationship between mTHPC fluorescence photobleaching and cell viability during in vitro photodynamic treatment of DP16 cells“ Photochem. Photobiol. 75, 289–95 (2002)
[Crossref] [PubMed]

Star, W.M

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
[Crossref] [PubMed]

Star, W.M.

D.J. Robinson, H.S. de Bruijn, W.J. de Wolf, H.J.C.M. Sterenborg, and W.M. Star. “Topical 5-aminolevulinic acid-photodynamic therapy of hairless mouse skin using two-fold illumination schemes: PpIX fluorescence kinetics, photobleaching and biological effect,” Photochem. Photobiol. 72,794–802 (2000)
[Crossref]

W.M. Star, “Light dosimetry in vivo,” Phys. Med. Biol. 42, 763–87 (1997).
[Crossref] [PubMed]

Sterenborg, H.J.C.M.

I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
[Crossref] [PubMed]

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H.J.C.M. Sterenborg, M. Janson, and M.J.C. van Gemert. “A novel frequency domain technique for measurement of triplet decay times using two diode lasers,” Phys.Med. Biol. 44, 1419–1426 (1999)
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Stringer, M.R.

D.J. Robinson, H.S. de Bruijn, N. van der Veen, M.R. Stringer, S.B. Brown, and W.M Star. “Fluorescence photobleaching of ALA-induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: the effect of light dose and irradiance and the resulting biological effect,” Photochem. Photobiol. 67, 140–9 (1998)
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I.A. Boere, D.J. Robinson, H.S. de Bruijn, J. van den Boogert, H.W. Tilanus, H.J.C.M. Sterenborg, and R.W. de Bruin. “Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy,” Photochem. Photobiol. 78, 271–7 (2003)
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M.J. Niedre, M.S. Patterson, and B.C. Wilson. “Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo,” Photochem. Photobiol. 75: 382–91 (2002)
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H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
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M.J. Niedre, A.J. Secord, M.S. Patterson, and B.C. Wilson. “In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy,” Cancer Res. 63, 7986–9 (2003)
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B.C. Wilson, M.S. Patterson, and L. Lilge “Implicit and Explicit Dosimetry in Photodynamic Therapy: A New Paradigm,” Lasers Med. Sci. 12, 182–99 (1997)
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H. Zeng, M. Korbelik, D.I. McLean, C. MacAulay, and H. Lui. “Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer,” Photochem. Photobiol. 75, 398–405 (2002)
[Crossref] [PubMed]

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Phys.Med. Biol. (1)

H.J.C.M. Sterenborg, M. Janson, and M.J.C. van Gemert. “A novel frequency domain technique for measurement of triplet decay times using two diode lasers,” Phys.Med. Biol. 44, 1419–1426 (1999)
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Supplementary Material (1)

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Figures (3)

Fig. 1.
Fig. 1. Emission spectrum of 10 μg Sn-Mesoporphyrin in 1% albumin at different pO2 levels.
Fig. 2.
Fig. 2. Phosphorescence/fluorescence ratio as a function of the pO2 (left). Measurements were made in a cuvette using a 100 μm sensor needle positioned at different distances from the air-liquid interface (see ratio image on right). The curve is the best fit of eq.4 with a critical pO2 of 26 mm Hg (see discussion).
Fig. 3.
Fig. 3. (2.74 MB) Movie (100 frames, 25 seconds per frame) of the phosphorescence fluorescence ratio during PDT in a thin cuvette with a few airbubbles. The dark areas represent high oxygen levels, while the grey areas with increased phosphorescence indicate a decrease in oxygen levels. The bar refers to the value of α (eq.4); The total width of the image is 4.7 mm (size 1.28 Mb).

Equations (13)

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[ N 0 ( t ) ] t = [ N 0 ( t ) ] B 01 Φ ( t ) + [ N 1 ( t ) ] ( A 10 + k 10 ) + [ N 2 ( t ) ] ( A 20 + k 20 + q [ 3 O 2 ( t ) ] )
[ N 1 ( t ) ] t = + [ N 0 ( t ) ] B 01 Φ ( t ) [ N 1 ( t ) ] ( A 10 + k 10 + k 12 )
[ N 2 ( t ) ] t = + [ N 1 ( t ) ] k 21 [ N 2 ( t ) ] ( A 20 + k 20 + q [ 3 O 2 ( t ) ] )
[ N 0 ] = N 00
[ N 1 ] = N 00 B 01 Φ ( A 10 + k 10 + k 12 )
[ N 2 ] = N 00 B 01 Φ k 21 ( A 20 + k 20 + q [ 3 O 2 ] ) ( A 10 + k 10 + k 12 )
Singlet Oxygen production = [ N 2 ] q [ 3 O 2 ]
α = q [ 3 O 2 ] ( A 20 + k 20 + q [ 3 O 2 ] )
F = A 10 [ N 1 ] = N 00 B 01 Φ A 10 ( A 10 + k 10 + k 12 )
P = A 20 [ N 2 ] = N 00 B 01 Φ A 20 k 21 ( A 20 + k 20 + q [ 3 O 2 ] ) ( A 10 + k 10 + k 12 )
P F = A 20 [ N 2 ] A 10 [ N 1 ] = A 20 k 21 A 10 ( A 20 + k 20 + q [ 3 O 2 ] ) = γ ( 1 α )
with γ = k 21 A 20 ( A 20 + k 20 ) A 10
[ 3 O 2 ] crit = A 20 + k 20 q

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