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Towards the Jablonski
Diagram for PDT In Vivo
Wilson, Brian1
Ontario Cancer Institute/University of Toronto, Canada1
Abstract-
The photophysical processes in photodynamic therapy (PDT) for most photosensitizers
used clinically are: photon absorption from the ground state (So) to
the first excited state (S1), intersystem crossing to the triplet state
(T1) and energy/spin exchange with ground state molecular oxygen (3O2)
to produce cytotoxic singlet state oxygen (1O2). While these steps,
described by the Jablonski diagram, are relatively straightforward to
measure in solution, there are significant theoretical and technological
problems in their determination in tissue in vivo, or even in cells
in vitro. In this presentation the status of techniques and corresponding
models for measuring each state will be critically examined. Thus, for
example, either diffuse reflectance spectroscopy or fluorescence spectroscopy
may be used to determine the ground-state concentration of photosensitizer,
given knowledge of the excitation light distribution. The triplet state
may be investigated using transient absorption spectroscopy, in a pump-probe
configuration, and its decay kinetics may yield the ground-state oxygen
concentration. As we have recently demonstrated, the singlet oxygen
may be measured by near-infrared luminescence decay. A major challenge
in all of these techniques is to make absolute measurements of the state
concentrations, given the confounding factors of high light scattering
and endogenous absorption of tissues. Approaches explored include both
spatially- and temporally-resolved spectroscopies. Individual techniques
raise specific additional issues, such as low signal levels due to low
transient concentrations (T1 and 1O2) that push the current technological
envelop. Barriers to successful implementation, both in the laboratory
and in the clinic will be considered. Speculation on future complicating
factors will include photosensitizers that have alternative or additional
excitation pathways and 2-photon PDT. The discussion will conclude by
considering how much of the Jablonski diagram one needs to determine
in order to be useful for improving PDT treatments.
Keywords: photodynamic,
Jablonski
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