In vivo PDT dosimetry: singlet oxygen emission and photosensitizer fluorescence

Photodynamic therapy (PDT) is a light activated chemotherapy that is dependent on three parameters: photosensitizer (PS) concentration; oxygen concentration; and light dosage. Due to highly variable treatment response, the development of an accurate dosimeter to optimize PDT treatment outcome is an important requirement for practical applications. Singlet oxygen is an active species in PDT, and we are developing two instruments, an ultra-sensitive singlet oxygen point sensor and a 2D imager, with the goal of a real-time dosimeter for PDT researchers. The 2D imaging system can visualize spatial maps of both the singlet oxygen production and the location of the PS in a tumor during PDT. We have detected the production of singlet oxygen during PDT treatments with both in-vitro and in-vivo studies. Effects of photobleaching have also been observed. These results are promising for the development of the sensor as a real-time dosimeter for PDT which would be a valuable tool for PDT research and could lead to more effective treatment outcome. We summarize recent results in this paper.

[1]  Tayyaba Hasan,et al.  In-vivo singlet oxygen dosimetry of clinical 5-aminolevulinic acid photodynamic therapy. , 2008, Journal of biomedical optics.

[2]  S. Lee,et al.  Detection of singlet oxygen production for PDT treatments both in vitro and in vivo using a diode laser-based singlet oxygen monitor , 2006 .

[3]  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.

[4]  Tayyaba Hasan,et al.  Pulsed diode laser-based singlet oxygen monitor for photodynamic therapy: in vivo studies of tumor-laden rats. , 2008, Journal of biomedical optics.

[5]  David Kessel,et al.  Mechanism of PDT-induced mitochondrial photodamage , 2001, SPIE BiOS.

[6]  M. Kuimova,et al.  Singlet oxygen in a cell: spatially dependent lifetimes and quenching rate constants. , 2009, Journal of the American Chemical Society.

[7]  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.

[8]  Tayyaba Hasan,et al.  Ultrasensitive diode-laser-based monitor for singlet oxygen , 2003, SPIE BiOS.

[9]  T J Dougherty,et al.  Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. , 1976, Cancer research.

[10]  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.

[11]  P B Cerrito,et al.  The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. , 1992, Cancer research.