Macroscopic modeling of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing
biological effects for type II photosensitizers during PDT. We have developed a macroscopic model to calculate reacted
singlet oxygen concentration ([1O2]rx for PDT. An in-vivo RIF tumor mouse model is used to correlate the necrosis
depth to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and
photosensitizer concentrations. Inputs to the model include 4 photosensitizer specific photochemical parameters along
with the apparent singlet oxygen threshold concentration. Photosensitizer specific model parameters are determined for
several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet oxygen threshold concentration is
approximately 0.41 - 0.56 mM for all three photosensitizers studied, assuming that the fraction of singlet oxygen
generated that interacts with the cell is (f = 1). In comparison, value derived from other in-vivo mice studies is 0.4 mM
for mTHPC. However, the singlet oxygen threshold doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro
EMT6/Ro spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of threshold singlet oxygen
dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanism on the
singlet oxygen threshold dose is discussed using the BPD with different drug-light intervals 3 hrs vs. 15 min. The
observed discrepancies between different experiments warrant further investigation to explain the cause of the
difference.
Photodynamic therapy (PDT) offers a cancer treatment modality capable of providing minimally invasive localized
tumor necrosis. To accurately predict PDT treatment outcome based on pre-treatment patient specific parameters, an
explicit dosimetry model is used to calculate apparent reacted 1O2 concentration ([1O2]rx) at varied radial distances
from the activating light source inserted into tumor tissue and apparent singlet oxygen threshold concentration for
necrosis ([1O2]rx, sd) for type-II PDT photosensitizers. Inputs into the model include a number of photosensitizer
independent parameters as well as photosensitizer specific photochemical parameters ξ σ, and β. To determine the
specific photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were treated with BPDPDT
with varied light source strengths and treatment times. All photosensitizer independent inputs were assessed
pre-treatment and average necrotic radius in treated tissue was determined post-treatment. Using the explicit
dosimetry model, BPD specific ξ σ, and β photochemical parameters were determined which estimated necrotic
radii similar to those observed in initial BPD-PDT treated mice using an optimization algorithm that minimizes the
difference between the model and that of the measurements. Photochemical parameters for BPD are compared with
those of other known photosensitizers, such as Photofrin. The determination of these BPD specific photochemical
parameters provides necessary data for predictive treatment outcome in clinical BPD-PDT using the explicit
dosimetry model.
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