A quantitative study of in vivo protoporphyrin IX fluorescence build up during occlusive treatment phases

C Louise Campbell,C Tom A Brown,Kenneth Wood,Ana Gabriela Salvio,Natalia M Inada,Vanderlei S Bagnato,Harry Moseley

doi:10.1016/j.pdpdt.2017.02.004

Abstract

BackgroundTopical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics. MethodsFluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3h long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models. ResultsIt was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type. ConclusionsThe study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.

Highlights

Topical photodynamic therapy (PDT) relies on the interaction between light, molecular oxygen and a photosensitive chemical to produce singlet oxygen and other reactive oxygen species (ROS), leading to tissue injury and death of targeted cells [1]
During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death
In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics

Summary

Introduction

Topical photodynamic therapy (PDT) relies on the interaction between light, molecular oxygen and a photosensitive chemical to produce singlet oxygen and other reactive oxygen species (ROS), leading to tissue injury and death of targeted cells [1]. After the application of the prodrug the lesion is covered with an occlusive dressing which blocks out any ambient light During this occlusive treatment (with a typical duration of three hours) the prodrug diffuses through the skin and is converted to the photosensitive molecule protoporphyrin IX (PpIX) in the tumour cells [3]. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics. Methods: Fluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3 hour long occlusive treatment prior to irradiation. The predictive models suggest that there is a significant difference in PpIX production between lesion location, no significant difference is demonstrated between different lesion types, gender and skin type

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