Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling

Abstract

Singlet oxygen (1O2) is the major cytotoxic agent responsible for cell killing for type-II photodynamic therapy (PDT). An empirical four-parameter macroscopic model is proposed to calculate the “apparent reacted 1O2 concentration”, [1O2]rx, as a clinical PDT dosimetry quantity. This model incorporates light diffusion equation and a set of PDT kinetics equations, which can be applied in any clinical treatment geometry. We demonstrate that by introducing a fitting quantity “apparent singlet oxygen threshold concentration” [1O2]rx,sd, it is feasible to determine the model parameters by fitting the computed [1O2]rx to the Photofrin-mediated PDT-induced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [1O2]rx,sd, we expect to use this model as an explicit dosimetry to assess PDT treatment outcome for a specific photosensitizer in an in vivo environment. The results also provide evidence that the [1O2]rx, because it takes into account the oxygen consumption (or light fluence rate) effect, can be a better predictor of PDT outcome than the PDT dose defined as the energy absorbed by the photosensitizer, which is proportional to the product of photosensitizer concentration and light fluence.

Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study

“…The tendency to have large variations in Photofrin uptake by the tumors is in agreement with the other studies. 18,40 The calculated ½ 1 O 2 rx did not follow the trend of increasing light dose or ϕ. Among the 11 PDT treatment groups with light ranging from 50 to 250 J∕cm 2 , the highest amount of ½ 1 O 2 rx was found with the group treated to 135 J∕cm 2 with 75 mW∕cm 2 .…”

“…18 Two parallel catheters were inserted into the tumor with one centrally positioned and the other a fixed distance away. A 2-mm point source fiber was coupled to the 630-nm diode laser, and light fluence profiles were obtained along the length of the second catheter using an isotropic detector.…”

“…18 The complete set of the reaction rate equations and their derivations have been described in detail elsewhere. 18,[29][30][31] In this model, the reaction rate equations are simplified as the following, which incorporates a set of PDT kinetic equations:…”

“…17 For this purpose, an empirical four-parameter macroscopic 1 O 2 model was developed, and the reacted singlet oxygen (½ 1 O 2 rx ) was proposed as a dosimetry quantity for the accumulated concentration of 1 O 2 that is responsible for cellular killing and clinical outcomes. 18 In this study, this model was adopted to evaluate the potential of using calculated ½ 1 O 2 rx as a dosimetric predictor for Photofrin-mediated PDT on tumor growth in a mouse tumor model.…”

PDT is better than alternative therapies such as brachytherapy, electron beams, or low‐energy x rays for the treatment of skin cancers

“…15 Quantitative models that describe the production of singlet oxygen are emerging. 16 Alternatively, implicit dosimetry 5 ͑e.g., fluorescent photobleaching͒ can be used for PDT dosimetry. 2 The fact that these methods of dosimetry are not currently in widespread use in PDT should be a cause for more physics involvement rather than a cause for discouragement of its clinical use.…”