Low-fluence rate, long duration photodynamic therapy in glioma mouse model using organic light emitting diode (OLED).
BACKGROUND
The treatment of gliomas poses significant clinical challenges due to resistance to chemo and radiation therapy, and treatment side effects. Metronomic photodynamic therapy (mPDT), which involves long treatment time with low fluence rate and multiple or continuous photosensitizer administrations, has potential in treating gliomas without threatening the quality of life and has been demonstrated in rats and rabbits. mPDT in small animals such as mouse is not yet shown due to lack of lightweight illumination device for long periods of time.


METHODS
We presented low fluence rate (3mW/cm(2)) and long duration (3.7h) PDT treatment in a nude mouse model of human glioblastoma by using organic light emitting diode (OLED) with single dose of 5-aminolevulinic acid (ALA) administration as photosensitizer. Tumor volume was measured using bioluminescent imaging and the animal survival time was recorded. Additionally, we have performed limited PDT dosimetric measurements of PpIX fluorescence, tumor oxygenation and hemoglobin concentration in 3 PDT mice.


RESULTS
For animals with similar pre- and immediate post-light tumor volume, the averaged total survival time of PDT mice is 40.5±9.2 days that are significantly longer than the control mice (26.0±2.0 days). The post-light survival time of PDT mice is 14.3±5.9 days that are marginally longer than the control group (8.0±0.0 days). In the dosimetric measurement, good maintenance of PpIX fluorescence in one PDT mouse has relatively improved survival time, compared with the other two PDT mice (i.e., 24 days versus 16 and 17 days).


CONCLUSIONS
This pilot study demonstrated the feasibility of low-fluence rate and long treatment time of ALA-PDT using OLED without anesthetization of animals. The response of PDT treated animals with similar pre- and post-light tumor volume is encouraging to show a longer survival time than the controls. The dosimetric indices such as photosensitizer fluorescence and tissue oxygenation would help understand the possible treatment barriers for further improvement of treatment plans.
Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan; Department of Physics, National Taiwan University, Taipei 106, Taiwan.
Han-Wen
HW
Guo
Department of Biomedical Imaging and Radiological Science, National Yang-Ming University, Taipei 112, Taiwan.
Liang-Ting
LT
Lin
Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan.
Po-Hsiung
PH
Chen
OLED Platform Technology Division, AU Optronics Corporation, Hsinchu 30078, Taiwan.
Meng-Huan
MH
Ho
OLED Platform Technology Division, AU Optronics Corporation, Hsinchu 30078, Taiwan.
Wan-Ting
WT
Huang
Department of Biomedical Imaging and Radiological Science, National Yang-Ming University, Taipei 112, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan.
Yi-Jang
YJ
Lee
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan.
Shih-Hwa
SH
Chiou
Division of Thoracic Surgery, Tao-Yuan General Hospital, Taoyuan County 300, Taiwan.
Yei-San
YS
Hsieh
Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan; Center for Quantum Science and Engineering, National Taiwan University, Taipei 106, Taiwan; Center for Optoelectronic Biomedicine of Medicine, National Taiwan University, Taipei 106, Taiwan. Electronic address: cydong@phys.ntu.edu.tw.
Chen-Yuan
CY
Dong
Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan; Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA. Electronic address: hwwang@umd.edu.
Hsing-Wen
HW
Wang
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010865:Pilot Projects; D011524:Protoporphyrins; D016019:Survival Analysis; D013997:Time Factors
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
5-Aminolevulinic acid (ALA); Gliomas; Metronomic photodynamic therapy (mPDT); Organic light emitting diode (OLED)