McIlroy, Brian William; (1998) Spectroscopic studies of photodynamic therapy related to real-time monitoring of dosimetry. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Photodynamic therapy (PDT) is a non-thermal technique for inducing tissue necrosis with light following the administration of a photosensitising drug. One of the main challenges facing PDT is the development of real-time monitoring techniques to improve the dosimetry since current clinical therapy relies purely on pre-determined drug and light doses. This thesis deals with the development of methods for monitoring PDT dosimetric parameters of tissue oxygenation and the photosensitiser concentration. Spectroscopic studies were carried out both in vitro and in vivo using the following photosensitisers: aluminium disulphonated phthalocyanine and 5-aminolaevulinic acid induced protoporphyrin IX (PpIX). The techniques of laser induced fluorescence spectroscopy and diffuse reflectance spectroscopy were employed and spectra were resolved using a charge-coupled device (CCD) spectrograph system. The CCD array was also used for fluorescence imaging of photosensitisers in tissue. These techniques were evaluated firstly using a stable tissue phantom material containing the photosensitiser. Studies were then carried out in tissue using fibre-optic probes and changes in the fluorescence and reflectance spectra were recorded during PDT. Both photosensitisers exhibited photobleaching and a fluorescent photoproduct could be detected with PpIX, both in animal and clinical biopsy specimens. Different kinetics were observed when the blood supply was occluded. A time-resolved approach for the study of tissue oxygenation during PDT was developed, relying on the oxygen-dependent phosphorescence quenching of a probe compound. A significant depletion in tissue oxygenation by up to a factor of ten was observed during PDT treatment with a smaller reduction at further distances from the treatment source light. The dependence of tissue autofluorescence during PDT was studied using ultraviolet excitation. A rapid decrease was observed in NADH fluorescence during PDT. The spectroscopic techniques developed in this project are capable of monitoring the effect of PDT on tissue, and with further development may provide a means of real-time monitoring of PDT for clinical use.

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