Monitoring oxygen concentration during photodynamic therapy using prompt photosensitizer fluorescence

A novel technique is described that uses either time-resolved or steady state prompt photosensitizer fluorescence to measure local oxygen concentration. Solution experiments conducted with Al(III) phthalocyanine chloride tetrasulfonic acid confirmed that the steady state fluorescence signal is dependent on the oxygen concentration and fluence rate. A relationship between prompt sensitizer fluorescence and sensitizer triplet quenching efficiency is derived which does not require knowledge of the Stern-Volmer constant. Similar relationships are also derived for sensitizer delayed fluorescence and phosphorescence. An explicit photodynamic therapy (PDT) dose metric that incorporates light dosimetry, sensitizer dosimetry, and triplet quenching efficiency is introduced. All components of this metric can be determined by optical measurements.

[1]  Ken Kang-Hsin Wang,et al.  Photodynamic dose does not correlate with long-term tumor response to mTHPC-PDT performed at several drug-light intervals. , 2008, Medical physics.

[2]  Michael S Patterson,et al.  Quantification of fluorophore concentration in vivo using two simple fluorescence-based measurement techniques. , 2005, Journal of biomedical optics.

[3]  T. Hasan,et al.  PHOTOPHYSICAL AND PHOTOSENSITIZING PROPERTIES OF BENZOPORPHYRIN DERIVATIVE MONOACID RING A (BPD‐MA) * , 1994, Photochemistry and photobiology.

[4]  Jarod C Finlay,et al.  Photobleaching kinetics of Photofrin in vivo and in multicell tumour spheroids indicate two simultaneous bleaching mechanisms. , 2004, Physics in medicine and biology.

[5]  Ken Kang-Hsin Wang,et al.  A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy. , 2006, Medical physics.

[6]  Filippo Piffaretti,et al.  Real-time, in vivo measurement of tissular pO2 through the delayed fluorescence of endogenous protoporphyrin IX during photodynamic therapy , 2012, Journal of biomedical optics.

[7]  Michael S Patterson,et al.  Singlet Oxygen Luminescence Dosimetry (SOLD) for Photodynamic Therapy: Current Status, Challenges and Future Prospects , 2006, Photochemistry and photobiology.

[8]  B W Pogue,et al.  Fiber-optic bundle design for quantitative fluorescence measurement from tissue. , 1998, Applied optics.

[9]  T. Foster,et al.  © 1999 Cancer Research Campaign Article no. bjoc.1998.0220 Hypoxia significantly reduces aminolaevulinic acidinduced , 2022 .

[10]  Mark A. Weston,et al.  Calculation of Singlet Oxygen Dose Using Explicit and Implicit Dose Metrics During Benzoporphyrin Derivative Monoacid Ring A (BPD‐MA)‐PDT In Vitro and Correlation with MLL Cell Survival , 2011, Photochemistry and photobiology.

[11]  G. Wagnières,et al.  Optical fiber-based setup for in vivo measurement of the delayed fluorescence lifetime of oxygen sensors. , 2011, Journal of biomedical optics.

[12]  Johannes Swartling,et al.  Realtime light dosimetry software tools for interstitial photodynamic therapy of the human prostate. , 2007, Medical physics.

[13]  Razvigor Darlenski,et al.  Photodynamic therapy in dermatology: past, present, and future , 2012, Journal of biomedical optics.

[14]  K. Berg,et al.  THE PHOTODEGRADATION OF PORPHYRINS IN CELLS CAN BE USED TO ESTIMATE THE LIFETIME OF SINGLET OXYGEN , 1991, Photochemistry and photobiology.

[15]  Qiyin Fang,et al.  Monitoring Photosensitizer Uptake Using Two Photon Fluorescence Lifetime Imaging Microscopy , 2012, Theranostics.

[16]  Michael S Patterson,et al.  A dynamic model for ALA-PDT of skin: simulation of temporal and spatial distributions of ground-state oxygen, photosensitizer and singlet oxygen , 2010, Physics in medicine and biology.

[17]  C. Koch,et al.  Photodynamic therapy creates fluence rate-dependent gradients in the intratumoral spatial distribution of oxygen. , 2002, Cancer research.

[18]  A. Ouzzane,et al.  Photodynamic therapy in urology: what can we do now and where are we heading? , 2012, Photodiagnosis and photodynamic therapy.

[19]  Michael S Patterson,et al.  Direct Near-infrared Luminescence Detection of Singlet Oxygen Generated by Photodynamic Therapy in Cells In Vitro and Tissues In Vivo¶ , 2002, Photochemistry and photobiology.

[20]  Jarod C Finlay,et al.  Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy. , 2005, Journal of photochemistry and photobiology. B, Biology.

[21]  J. Kanofsky,et al.  QUENCHING OF SINGLET OXYGEN BY BIOMOLECULES FROM L1210 LEUKEMIA CELLS , 1992, Photochemistry and photobiology.

[22]  Michael S Patterson,et al.  Calculation of Singlet Oxygen Dose from Photosensitizer Fluorescence and Photobleaching During mTHPC Photodynamic Therapy of MLL Cells ¶ , 2005, Photochemistry and photobiology.

[23]  T. Foster,et al.  Photochemical oxygen consumption sensitized by a porphyrin phosphorescent probe in two model systems. , 2000, Biophysical journal.

[24]  Michael S Patterson,et al.  Characterization of Photofrin photobleaching for singlet oxygen dose estimation during photodynamic therapy of MLL cells in vitro , 2005, Physics in medicine and biology.

[25]  Michael S Patterson,et al.  In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy. , 2003, Cancer research.

[26]  Kai Zhang,et al.  Techniques for delivery and monitoring of TOOKAD(WST09)-mediated photodynamic therapy of the prostate: clinical experience and practicalities , 2005, SPIE BiOS.

[27]  H Anholt,et al.  PHTHALOCYANINE FLUORESCENCE IN TUMORS DURING PDT , 1990, Photochemistry and photobiology.

[28]  B. Wilson,et al.  The Influence of Oxygen Depletion and Photosensitizer Triplet‐state Dynamics During Photodynamic Therapy on Accurate Singlet Oxygen Luminescence Monitoring and Analysis of Treatment Dose Response , 2011, Photochemistry and photobiology.

[29]  M G Nichols,et al.  The Mechanism of Photofrin Photobleaching and Its Consequences for Photodynamic Dosimetry , 1997, Photochemistry and photobiology.

[30]  V. S. Bagnato,et al.  Photodynamic therapy induced vascular damage: an overview of experimental PDT , 2013 .

[31]  M. Sinaasappel,et al.  Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo. , 1996, Journal of applied physiology.

[32]  T. Zhu,et al.  Point/counterpoint. PDT is better than alternative therapies such as brachytherapy, electron beams, or low-energy x rays for the treatment of skin cancers. , 2011, Medical physics.

[33]  L. Lilge,et al.  Implicit and explicit dosimetry in photodynamic therapy: a New paradigm , 1997, Lasers in Medical Science.

[34]  Michael S. Patterson,et al.  Calculation of Singlet Oxygen Dose from Photosensitizer Fluorescence and Photobleaching During mTHPC Photodynamic Therapy of MLL Cells¶ , 2005 .

[35]  Michael S Patterson,et al.  Photobleaching kinetics, photoproduct formation, and dose estimation during ALA induced PpIX PDT of MLL cells under well oxygenated and hypoxic conditions , 2006, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[36]  Michael S Patterson,et al.  Insights into photodynamic therapy dosimetry: simultaneous singlet oxygen luminescence and photosensitizer photobleaching measurements. , 2012, Biophysical journal.

[37]  C. Ozcakir-Tomruk,et al.  Photodynamic therapy in dentistry: a literature review , 2012, Clinical Oral Investigations.

[38]  Thomas H Foster,et al.  Photophysical Parameters, Photosensitizer Retention and Tissue Optical Properties Completely Account for the Higher Photodynamic Efficacy of meso-Tetra-Hydroxyphenyl-Chlorin vs Photofrin¶ , 2005, Photochemistry and photobiology.

[39]  A. Pawlak,et al.  Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells. , 2006, Biochemical and biophysical research communications.

[40]  B. Wilson,et al.  The physics, biophysics and technology of photodynamic therapy , 2008, Physics in medicine and biology.

[41]  Brian C. Wilson,et al.  Techniques for delivery and monitoring of TOOKAD (WST09)-mediated photodynamic therapy of the prostate: clinical experience and practicalities. , 2005 .

[42]  M S Patterson,et al.  Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid , 2005, British Journal of Cancer.

[43]  S. Bishop,et al.  Excited triplet state photophysics of the sulphonated aluminium phthalocyanines bound to human serum albumin. , 1997, Journal of photochemistry and photobiology. B, Biology.

[44]  S B Malkowicz,et al.  Preliminary results of interstitial motexafin lutetium‐mediated PDT for prostate cancer , 2006, Lasers in surgery and medicine.

[45]  H. Heimann,et al.  Evaluation of verteporfin pharmakokinetics – redefining the need of photosensitizers in ophthalmology , 2012, Expert opinion on drug metabolism & toxicology.

[46]  T. Foster,et al.  Singlet Oxygen‐Versus Nonsinglet Oxygen‐Mediated Mechanisms of Sensitizer Photobleaching and Their Effects on Photodynamic Dosimetry , 1998, Photochemistry and photobiology.