Novel applications of diagnostic X-rays in activating photo-agents through X-ray induced visible luminescence from rare-earth particles: An in-vitro study

摘要

Photodynamic agents such as Photofrin II (Photo II) utilized in photodynamic therapy (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 II and type I mechanistic pathways through extensive generation of reactive oxygen species (ROS):rnsinglet oxygen O_2; superoxide anion O_2 ; and hydrogen peroxide H_2O_2; within the intra-tumoral environment. Unfortunately; due to shallow visible light penetration depth (~2mm to 5mm) in tissues; the PDT strategy currently has largely been restricted to the treatments 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. In this communication; we report on a novel strategy in utilizing "soft" energy diagnostic X-rays to indirectly activate Photo II through X-ray induced luminescence from Gadolinium oxysulfide (20 micron dimension) particles doped with Terbium: Gd_2O_2S:Tb. X-ray induced visible luminescence from Gd_2O_2S:Tb particles was spectroscopically characterized and the ROS production levels from clinically relevant concentration (10 fag/ml) of Photo II was quantified through changes in the Vitamin C absorbance. ROS kinetics through X-ray induced luminescence was found to be similar to the ROS kinetics from red He-Ne laser exposures used in the clinics. Taken together; 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.