Modelling fluorescence in clinical photodynamic therapy.

Understanding the interactions of non-ionizing radiation with living organisms has been the focus of much research over recent decades. The complex nature of these interactions warrants development of theoretical and experimental studies to gain an insight into predicting and monitoring the success of photodynamic therapy (PDT) protocols. There is a major impetus towards evidence-based recommendations for patient diagnosis, treatment and management. Knowledge of the biophysical aspects of PDT is important for improving dosimetry protocols. Fluorescence in clinical PDT may be used to detect and diagnose pre-malignant and malignant conditions, while photobleaching can monitor changes in fluorescence during treatment. Combining empirical fluorescence photobleaching clinical data with computational modelling enables clinical PDT dosimetry protocols to be investigated with a view to optimising treatment regimes. We will discuss how Monte Carlo radiation transfer (MCRT) modelling has been intercalated in the field of fluorescence detection and PDT. In this paper we highlight important aspects of basic research in PDT by reporting on the current utilisation of fluorescence in clinical PDT from both a clinical and theoretical perspective. Understanding and knowledge of light propagation in biological tissue from these perspectives should have a positive impact on treatment planning.

A novel light source with tuneable uniformity of light distribution for artificial daylight photodynamic therapy.

OBJECTIVES: Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and comparable treatment times to dPDT. Uniform light distribution across the target area is desirable in effective treatment planning, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. METHODS: Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighted spectra of both the light source and daylight match. The uniformity of the light distribution is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. RESULTS: The PpIX-weighted spectrum of the novel light source matches the PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. CONCLUSIONS: We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces.

Monte Carlo modeling of in vivo protoporphyrin IX fluorescence and singlet oxygen production during photodynamic therapy for patients presenting with superficial basal cell carcinomas.

We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, ß of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 ± 1 J/cm(2). Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm(2) could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.

A quantitative comparison of 5-aminolaevulinic acid- and methyl aminolevulinate-induced fluorescence, photobleaching and pain during photodynamic therapy.

The characteristics of protoporphyrin IX (PPIX) fluorescence in superficial basal cell carcinoma (sBCC) and carcinoma in situ (Bowen's Disease, BD) following application of 5-aminolaevulinic acid (5-ALA) and its methyl ester (methyl aminolevulinate [MAL]) before, during and after photodynamic therapy (PDT) were investigated in 40 patients. Photosensitizer prodrug penetration can limit PDT efficacy and understanding the characteristics of PPIX fluorescence through fluorescence spectroscopy, may improve knowledge of photosensitizer delivery. Fluorescence intensity was assessed quantitatively, and the rate of photobleaching was determined by fitting an exponential decay. As a secondary end-point, PDT-induced pain was also measured continuously during treatment using a novel hand-held device, known as a pain logger. In vivo PPIX fluorescence was shown to decrease during irradiation, allowing the in vivo photobleaching of PPIX to be monitored. No significant difference was found between ALA- or MAL-induced PPIX fluorescence in lesions of sBCC and BD (P>0.05), indicating no detectable difference in PPIX kinetics for the two prodrugs as assessed by these measures. Pain, as assessed by the logger device, showed high interindividual variability and pain levels tended to be higher initially, decreasing during treatment. No difference was seen in pain experienced during ALA-or MAL-PDT (P>0.05).