eprintid: 1445959
rev_number: 8
eprint_status: archive
userid: 636
dir: disk0/01/44/59/59
datestamp: 2017-07-07 13:52:12
lastmod: 2017-07-07 13:52:12
status_changed: 2017-07-07 13:52:12
type: thesis
metadata_visibility: show
item_issues_count: 0
creators_name: Woodhams, JH
title: Studies of photodynamic therapy: Investigation of physiological mechanisms and dosimetry
ispublished: unpub
note: Thesis digitised by ProQuest.
abstract: Photodynamic therapy (PDT) is a treatment for a range of malignant and benign lesions using light activated photosensitising drugs in the presence of molecular oxygen. PDT causes tissue damage by a combination of processes involving the production of reactive oxygen species (in particular singlet oxygen). Since the PDT cytotoxic effect depends on oxygen, monitoring of tissue oxygenation during PDT is important for understanding the basic physiological mechanisms and dosimetry of PDT. This thesis describes the use of non-invasive, optical techniques based on visible light reflectance spectroscopy for the measurement of oxy- to deoxyhaemoglobin ratio or haemoglobin oxygen saturation (HbSat). HbSat was monitored at tissue sites receiving different light dose during aluminium disulphonated phthalocyanine (AIS2PC) PDT. Results are presented on real time PDT-induced changes in HbSat in normal tissue (rat liver) and experimental tumours, and its correlation with the final biological effect under different light regimes, including fractionated light delivery. It was found to some extent that changes in HbSat could indicate whether the tissue would be necrotic after PDT and it was concluded that online physiological dosimetry is feasible for PDT. The evaluation of a new photosensitiser for PDT called palladium-bacteriopheophorbide (WST09) has been carried out in normal and tumour tissue in vivo. WST09 was found to exert a strong PDT effect but was active only shortly after administration. WST09 produced substantial necrosis in colonic tumours whilst only causing a small amount of damage to the normal colon under certain conditions indicating a degree of selectivity. Combination therapy with PDT for enhancing the extent of PDT-induced damage has been investigated in vivo by using the photochemical internalisation (PCI) technique and Type 1 mechanism enhanced phototoxicity with indole acetic acid (IAA). PCI of gelonin using AIS2PC PDT in vivo after systemic administration of gelonin was shown to enhance the effect of PDT in normal liver. The use of PDT and IAA did not result in a synergistic response.
date: 2006-01-31
id_number: PQ ETD:593283
oa_status: green
full_text_type: other
thesis_class: doctoral_open
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 306
institution: UCL (University College London)
department: Department of Surgery
thesis_type: Doctoral
citation:        Woodhams, JH;      (2006)    Studies of photodynamic therapy: Investigation of physiological mechanisms and dosimetry.                   Doctoral thesis , UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1445959/1/Woodhams_thesis.pdf