Novel applications of diagnostic X-rays in activating a clinical
photodynamic drug: Photofrin II through X-ray induced visible luminescence from
"rare-earth" formulated particles
Affiliations: Department of Electrical and Computer Engineering,
George Washington University, Washington, DC, USA | Intelligent Materials, Inc., Princeton, NJ, USA | U.S. Food and Drug Administration, Silver Spring, MD, USA
Note: [] Corresponding author: Erkinay Abliz, U.S. Food and Drug
Administration, White Oak campus, Silver Spring, MD, USA. E-mail: [email protected]
Abstract: 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:
Gd_{2}O_{2}S: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}O_{2}, superoxide anion O_{2}^{-},
and hydrogen peroxide H_{2}O_{2}, 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
Gd_{2}O_{2}S:Tb particles were spectroscopically characterized, and the
potential in-vitro cellular cytotoxicity of Gd_{2}O_{2}S:Tb particles on
human glioblastoma cells (due to 48 Hrs Gd_{2}O_{2}S:Tb particle exposure)
was screened through the MTS cellular metabolic assay. In-vitro human
glioblastoma cellular exposures in presence of Photo II with
Gd_{2}O_{2}S: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
Gd_{2}O_{2}S: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.
Keywords: X-ray induced luminescence, photodynamic therapy, reactive oxygen species detection, singlet oxygen, Photofrin II, Gadolinium Oxysulfide particles
