Current status of photodynamic therapy in oncology

Abstract

Photodynamic therapy (PDT) is a cancer treatment based on the accumulation in malignant tissue of a photosensitiser with low systemic toxicity. Subsequent illumination induces a type II photochemical reaction with singlet oxygen production that results in destruction of biomolecules and subcellular organelles. The first full clinical report of PDT dates from 1976. Haematoporphyrin derivative, a complex mixture of porphyrins, was initially used as a photosensitiser. An enriched fraction (porfimer sodium) is now the most commonly used clinical agent. After systemic administration porphyrins bind to albumin and lipoproteins. Accumulation occurs mainly in tumours and organs of the reticuloendothelial system. The light of an argon-dye laser can be tuned to the appropriate wavelength and delivered either superficially, interstitially or intraluminally. Light distribution can be assessed by using a radiation transport model and tissue optical properties, or direct measurement with light detectors. The effects of PDT depend in a complex way on: characteristics, tissue concentration and localisation of the photosensitiser; the target tissue optical properties and oxygenation; activation wavelength, power density and treatment regimen. Future research is directed towards: better photosensitisers (i.e. phthalocyanines, chlorins or protoporphyrin IX endogenously produced from 5-aminolevulinic acid); improved light generation and delivery; and combination with hyperthermia, chemotherapy, radiotherapy or surgery. Adjuvant intraoperative PDT is a promising approach to destroying residual tumour after surgery.