Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of 50 mW/cm2 may consume 3O2 at rates as high as 6-9 microM s-1. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize 1O2-mediated damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with 360 J/cm2 delivered at 50 mW/cm2 compared to the same light dose delivered at 200 mW/cm2. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.
The rate or yield of resonance electronic excitation transfer is an important tool of biological research, used to estimate distances between chromophores. Besides the interchromophore distance, this rate or yield depends on several other parameters that are clearly important for determining the correct distances. In particular, in a medium characterized by a refractive index n, the expression for the rate contains a factor n -4 . We argue here that the correct value for n is that of the donor-acceptor intervening medium, not that of the overall solvent, as has been argued by some. The choice is clearly important to any quantitative application of the theory since the index of typical relevant materials ranges from 1.3 to 1.6. Incidental to our analysis, a certain expression that connects dipole strengths with radiative lifetimes requires correction. This leads to revisions of estimates of the amounts of exciton delocalization in antenna complexes from purple bacteria (downward by 25%). In our analysis we distinguish three physically distinct ways in which refractive index affects the rate and suggest how they should be handled.
Measurements of dipole strengths of chlorophylls in solution are reviewed and correlated. The refractive index dependence is found to be expressible in a simple empirical fashion that does not rely on the concept of vacuum dipole strength. The index dependence in some respects contradicts the dependence expected on the basis of effective field theories.
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