John G. Parker

Optical monitoring of singlet oxygen generation during photodynamic treatment of tumors

The author reports optical detection of singlet oxygen production accompanying continuous-wave (CW) laser irradiation of subcutaneous murine tumors at 630 nm following prior intraperitoneal injection of a Photofrin II sensitizer. The detection method is optical, remote, and, thus, noninvasive. Chopping of the incident laser beam was required in order to separate the spectrally discrete, time-delayed, singlet oxygen emission from the dominant, spectrally diffuse, coherent background provided by the combination of sensitizer infrared fluorescence and tissue-related autofluorescence. Using the infrared fluorescence to provide a reference, the singlet oxygen emission is shown to be given directly by the frequency-dependent quadrature component of the detector output. Maximum detector quadrature output for the in vivo case was obtained for a chopping frequency between 10 and 20 kHz. The spectral variation of the emission from the tumor was obtained and identified as that characteristic of singlet oxygen.

Factors of importance in the generation of singlet oxygen during photodynamic treatment of tumors

Photodynamic therapy (PDT), a relatively new treatment for cancer, has evolved from the investigational stage and is now being evaluated clinically for certain cancer types under FDA-approved protocols. Results obtained to date indicate the treatment to be promising, however, not without limitations. This therapy involves the cooperative action of an injectable tumor-specific sensitizer and light, usually provided by the output of a laser. The general view, supported by a large body of in vitro data, is that the most important agent of tumor destruction is electronically excited oxygen (singlet oxygen) generated by a favored energy transfer from the optically excited sensitizer to ambient ground state oxygen. It is clear, therefore, that to understand the limitations of PDT in cancer treatment one has to fully understand the nature of singlet oxygen (102) interactions in the in vivo environment. This, of course, first requires an appropriate means for 102 detection and measurement. The recent demonstration in this laboratory that in vivo 102 detection during photodynamic treatment of tumors is indeed possible opens up this possibility.