Implicit and explicit dosimetry in photodynamic therapy: a New paradigm

Abstract

Dosimetry for photodynamic therapy (PDT) is becoming increasingly complex as more factors are identified which may influence the effectiveness of a given treatment. The simple prescription of a PDT treatment in terms of the administered photosensitizer dose, the incident light and the drug-light time interval does not account for patient-to-patient variability in either the photosensitizer uptake, tissue optical properties or tissue oxygenation, nor for the interdependence of the photosensitizer-light-tissue factors. This interdependence is examined and the implications for developing adequate dosimetry for PDT are considered. The traditional dosimetric approach, measuring each dose factor independently, and termed here 'explicit dosimetry', may be contrasted with the recent trend to use photosensitizer photobleaching as an index of the effective delivered dose, termed here 'implicit dosimetry'. The advantages and limitations of each approach are discussed, and the need to understand the degree to which the photobleaching mechanism is linked, or 'coupled', to the photosensitizing mechanism is analysed. Finally, the influence of the tissue-response endpoints on the optimal dosimetry methods is considered.

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

“…12 As indicated in this study, PDT dose was more correlated to CI than fluence with a goodness of fit of R 2 ¼ 0.79. However, CI was not always improved with increasing PDT dose.…”

“…This method of clinical dosimetry does not take into account the absorption and scattering of light or the uptake of the photosensitizer in the target tissue. 12 This might be responsible for the unpredictable response and variability between clinical dosimetry and PDT outcome. 13,14 To find a better solution for PDT dosimetry, explicit PDT dosimetry has been introduced.…”

“…PDT dose may serve as a good predictor of outcome in 3 O 2 enriched conditions. 12 However, in hypoxic conditions, it becomes less accurate for predicting the PDT efficacy since it does not consider the rate of PDT consumption of 3 O 2 for different ϕ. 15,16 With integration of the variation of 3 O 2 concentration (½ 3 O 2 ) into explicit dosimetry, a so-called singlet oxygen explicit dosimetry method based on mathematical modeling to calculate the 1 O 2 has made it possible to predict the PDT outcome.…”

The role of photodynamic therapy (PDT) physics

“…Explicit dosimetry refers to the prediction of singlet oxygen dose on the basis of measurable quantities that contribute to the photodynamic effect. 31 The quantities of interest are typically the distributions of light, photosensitizer, and oxygen. The distributions of photosensitizer and oxygenation can be measured via optical spectroscopy, as described above.…”

“…Direct dosimetry relies on the detection of singlet oxygen itself, either through its own phosphorescence emission or via singlet-oxygen- sensitive chromophores. Implicit dosimetry 31 uses a quantity such as fluorescence photobleaching of the photosensitizer, which is indirectly predictive of the production of singlet oxygen. Strategies for direct and implicit dosimetry are under development and will be discussed in later sections.…”