Insights into Photodynamic Therapy Dosimetry: Simultaneous Singlet Oxygen Luminescence and Photosensitizer Photobleaching Measurements

Photodynamic therapy (PDT) is generally based on the generation of highly reactive singlet oxygen (1O2) through interactions of photosensitizer, light, and oxygen (3O2). These three components are highly interdependent and dynamic, resulting in variable temporal and spatial 1O2 dose deposition. Robu...

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Bibliographic Details
Published in:Biophysical journal 2012-02, Vol.102 (3), p.661-671
Main Authors: Jarvi, Mark T., Patterson, Michael S., Wilson, Brian C.
Format: Article
Language:English
Subjects:
anaerobic conditions
Bleaching
chlorins
Clinical outcomes
cytotoxicity
dose response
Dosimeters
Dosimetry
Dynamics
Emission
Fluorescence
Light therapy
Luminescence
Luminescent Measurements
Oxygen
Photobleaching
Photochemotherapy
Photodynamic therapy
Photosensitizing Agents - chemistry
Radiometry
Singlet oxygen
Singlet Oxygen - chemistry
Spectroscopy, Imaging, and Other Techniques
therapeutics
Time Factors
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Summary:Photodynamic therapy (PDT) is generally based on the generation of highly reactive singlet oxygen (1O2) through interactions of photosensitizer, light, and oxygen (3O2). These three components are highly interdependent and dynamic, resulting in variable temporal and spatial 1O2 dose deposition. Robust dosimetry that accounts for this complexity could improve treatment outcomes. Although the 1270 nm luminescence emission from 1O2 provides a direct and predictive PDT dose metric, it may not be clinically practical. We used 1O2 luminescence (or singlet oxygen luminescence (SOL)) as a gold-standard metric to evaluate potentially more clinically feasible dosimetry based on photosensitizer bleaching. We performed in vitro dose-response studies with simultaneous SOL and photosensitizer fluorescence measurements under various conditions, including variable 3O2, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). The results show that SOL was always predictive of cytotoxicity and immune to PDT's complex dynamics, whereas photobleaching-based dosimetry failed under hypoxic conditions. However, we identified a previously unreported 613 nm emission from mTHPC that indicates critically low 3O2 levels and can be used to salvage photobleaching-based dosimetry. These studies improve our understanding of PDT processes, demonstrate that SOL is a valuable gold-standard dose metric, and show that when used judiciously, photobleaching can serve as a surrogate for 1O2 dose.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2011.12.043