Photodynamic therapy: An update

Abstract

The cytotoxic potential of photosensitisers has been known for more than half a century, but it is only in the last decade or so that it has been studied in much greater depth and evaluated critically in both laboratory and clinical settings. Photodynamic therapy (PDT) usually involves the systemic administration of a photosensitiser which is retained with some selectivity in tumour tissue when compared with the normal tissue from which the tumour arose. The drug is then photoactivated by light of the appropriate wavelength matched to the absorption characteristic of the photosensitiser used. This leads to localized tumour necrosis, which is primarily consequent to vascular collapse [1,2]. At the doses used, neither the drug alone nor the light alone produces a cytotoxic response. The porphyrins do not necessarily accumulate within malignant tumour cells but photosensitiser is found preferentially concentrated around turnout blood vessels. The photochemical reaction gives rise to a highly active singlet oxygen species capable of causing cell death. The lifetime of singlet oxygen, is too short for it to move more than a few cell diameters from its site of production, so that the cytotoxic effect is confined to areas of high sensitiser concentration. The concept of truly selective tumour necrosis was one of the exciting aspects of PDT. However, the best selectivity of uptake of either the porphyrins or the phthalocyanines gives ratios of 2-3:1 [3] between tumours and adjacent normal tissue, except in intracranial tumours where it reaches 28:1. Truly selective necrosis depends then more on differential normal tissue healing, differential distribution of light between tumour and normal tissue (delivered interstitially for example), and differential photodegradation. Moreover, healing after PDT is certainly remarkable and would seem to be by regeneration rather than scarring [4]. The majority of clinical studies have involved haematoporphyrin derivative (HPD) as the photosensitiser. This is both an unsatisfactory and complex variable mixture of porphyrin monomers, dimers, polyrhers and aggregates; it is therefore difficult to ensure its reproducibility. The fraction of HPD which is responsible for its turnout localizing properties is the aggregated fraction. An enriched aggregate form