Assessment of singlet oxygen dosimetry concepts in photodynamic therapy through computational modeling

Abstract

Background: In photodynamic therapy (PDT) oxygen plays a vital role in killing tumor cells. Therefore oxygen dosimetry is being thoroughly studied.

Methods: Light distribution into tissue is modelled for radiation-induced fibrosarcoma (RIF) and nodular basal cell carcinoma (nBCC), in order to study the influence of blood flow on singlet oxygen concentration effectively leading to cell death ([¹O₂]_rx) from PDT, within this light distribution. This is achieved through initial oxygen supply rate (g₀) and initial molecular oxygen concentration ([³O₂]₀) calculations. Monte Carlo simulations and mathematical models are used for spatial and temporal distributions of [¹O₂]_rx. Hypoxia conditions are simulated by minimizing [³O₂]₀ and g₀. Furthermore, an optimization algorithm is developed to calculate minimum initial molecular oxygen concentration needed ([³O₂]_0,min) for constant [¹O₂]_rx, when blood flow changes.

Results: Our results validate that in initially well-oxygenated scenarios with normal blood flow maximum [¹O₂]_rx values are significantly higher than corresponding values of hypoxic scenarios both for RIF and nBCC models, with maximum oxygen supply rate percentage variations being independent from g₀. Moreover, [¹O₂]_rx appears to be more affected by an increase of g₀ than of [³O₂]₀ values. For low blood flow there is a linear relationship between [³O₂]_0,min and g₀, while for better oxygenated areas high blood flow reduces [³O₂]_0,min needed in exponential manner.

Conclusions: Blood flow appears to be able to compensate for oxygen consumption. The developed optimization protocol on oxygen dosimetry offers a suitable combination of [³O₂]_0,min and g₀ to achieve constant [¹O₂]_rx, despite possible blood flow variations.

Keywords: Blood flow; Hypoxia; Oxygen supply rate; Photodynamic therapy.