Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

Abstract

Excited-state singlet oxygen (1O2), generated during photodynamic therapy (PDT), is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR) luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC) in an animal model comprising luciferase- and green fluorescent protein (GFP)-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

Keywords

• Photodynamic therapy
• singlet oxygen luminescence dosimetry
• bioluminescence