Photodynamic therapy (PDT) is an effective therapeutic modality that uses a light source to activate light-sensitive photosensitizers to treat both oncologic and nononcological indications. Photosensitizers are excited to the long-lived triplet state, and they react with biomolecules via type I or II mechanism resulted in cell death and tumor necrosis. Free radicals and radical ions are formed by electron transfer reactions (type I), which rapidly react with oxygen leading to the production of reactive oxygen species (ROS), including superoxide ions, hydroxyl radicals and hydrogen peroxide. Singlet molecular oxygen is produced in a Type II reaction, in which the excited singlet state of the photosensitizer generated upon photon absorption by the ground-state photosensitizer molecule undergoes intersystem crossing to a long-lived triplet state. In this talk, the fundmental mechanisms and detection techniques for ROS generation in PDT will be introduced. In particular, the quantification of singlet oxygen generation for pre-clinical application will be highlighted, which plays an essential role in the establishment of robust singlet oxygen-mediated PDT dosimetry.
Vascular targeted photodynamic therapy (V-PDT) has been widely utilized for the prevention or treatment of
vascular-related diseases, including age-related macular degeneration, port-wine stains and prostate cancer. In order to
quantitative assessment the blood vessel damage during V-PDT, nude mice were implanted with Titanium dorsal skin
window chambers for in vivo V-PDT studies. For treatments, various irradiances including 50, 75, 100 and 200 mW/cm2
provided by a 532 nm semiconductor laser were performed with the same total light dose of 30 J/cm2 after the mice were
intravenously injection of Rose Bengal for 25 mg/Kg body weight. Laser speckle imaging and microscope were used to
monitor blood flow dynamics and vessel constriction during and after V-PDT, respectively. The V-PDT induced vessel
damages between different groups were compared. The results show that significant difference in blood vessel damage was
found between the lower irradiances (50, 75 and 100 mW/cm2) and higher irradiance (200 mW/cm2), and the blood vessel
damage induced by V-PDT is positively correlated with irradiance. This study implies that the optimization of irradiance is
required for enhancing V-PDT therapeutic efficiency.
In this study, the vessel constriction was measured as a biological indicator of acute vascular response after vascular
targeted photodynamic therapy (V-PDT). During V-PDT treatment, the near-infrared (NIR) singlet oxygen (1O2)
luminescence at 1270 nm generated in blood vessels in a dorsal skinfold window chamber model in vivo was directly
monitored using a custom built high-sensitive NIR imaging system. In order to compare the acute vascular response,
various irradiances with the same light dose were utilized for treatments. The obtained results show that the complete
arteriole constriction occurred frequently, while some of the larger veins were constricted partially. For the vessels that
have significant constriction after V-PDT, our preliminary data suggest that the vasoconstriction in the selected ROIs are
roughly correlated with the local cumulative 1O2 luminescence intensities. This study implies that the 1O2 luminescence
dosimetry maybe also effective for evaluating V-PDT efficiency.
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