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Civilizations in antiquity have endeavored to champion the use of light to treat illnesses in the human body. Although laser light has unique applications in medicine, its mechanism of action for low intensity exposures on cells, tissues, and the body continues to be controversial after nearly 50 years of investigations. This paper presents evidence for visible red and near infrared light to induce (indirect) generation of hydrogen peroxide as an important chemical messenger behind the stimulatory and inhibitory responses observed to low intensity light exposures. It is hypothesized that other ionizing or non-ionizing modalities can either directly or indirectly induce / or generate H 2 O 2 in an aqueous environment and could also bring about similar stimulatory or inhibitory bioeffects. One salient parameter which governs the bio-response is the level of generated H 2 O 2 . The authors discuss the mechanism which enables a small amount of hydrogen peroxide generated by light to produce beneficial effects.

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Steady state fluorescence polarization spectra and time-resolved emission decay kinetics have been measured in vitro from malignant and normal rat kidney tissue. The degrees of polarization and emission lifetimes from the cancerous and normal systems are different. The spectroscopic differences are attributed to environmental transformations local to the native flavin and porphyrin fluorophors' binding sites.

Introduction: In this communication we report on a novel non-invasive methodology in utilizing "soft" energy diagnostic X-rays to indirectly activate a photo-agent utilized in photodynamic therapy (PDT): Photofrin II (Photo II) through X-ray induced luminescence from Gadolinium Oxysulfide (20 micron dimension) particles doped with Terbium: Gd2O2S:Tb. Photodynamic agents such as Photo II utilized in PDT possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through (visible light) photon absorption, the agents exert their cellular cytotoxicity through type I and type II pathways through extensive generation of reactive oxygen species (ROS); namely, singlet oxygen 1 O2, superoxide anion O − 2 , and hydrogen peroxide H2O2, within the intra-tumoral environment. Unfortunately, due to shallow visible light penetration depth (∼ 2 mm to 5 mm) in tissues, the current PDT strategy has largely been restricted to the treatment of surface tumors, such as the melanomas. Additional invasive strategies through optical fibers are currently utilized in getting the visible light into the intended deep seated targets within the body for PDT.Methods: X-ray induced visible luminescence from Gd2O2S:Tb particles were spectroscopically characterized, and the potential in-vitro cellular cytotoxicity of Gd2O2S:Tb particles on human glioblastoma cells (due to 48 Hrs Gd2O2S:Tb particle exposure) was screened through the MTS cellular metabolic assay. In-vitro human glioblastoma cellular exposures in presence of Photo II with Gd2O2S:Tb particles were performed in the dark in sterile 96 well tissue culture plates, and the corresponding changes in the metabolic activities of the glioblastoma due to 15 minutes of (diagnostic energy) X-ray exposure was determined 48 Hrs after treatment through the MTS assay.Results: Severe suppression (> 90% relative to controls) in the cellular metabolic activity of human glioblastoma was measured due to the treatment of clinically relevant concentrations of 20 µg/ml Photo II, with Gd2O2S:Tb particles, and (120 kVp) diagnostic X-rays. Taken together, the in-vitro findings herein provide the basis for future studies in determining the safety and efficacy of this non-invasive X-ray induced luminescence strategy in activating photo-agent in deep seated tumors.

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