Early and recent events in the history of PDT and PD

BATLLE, ALCIRA

Buenos Aires, Argentina

Conferencia; 5th International Workshop on Photdynamic Therapy and Photodetection with Porphyrin precursosrs; 2006

Alcira Batlle, Qian Peng

Aminolevulinic acid (ALA) is the first committed intermediate in the biosynthesis of porphyrins. Protoporphyrin IX (PPIX), a natural photosensitiser, can be synthesized from ALA. Uses of ALA: ALA has been used as a biodegradable herbicide (1984), as an insecticide (1988) and as a growth regulator (2001) in plants. The use of endogenous PPIX generated from ALA has led to many applications in Photodynamic Therapy (PDT) and Photodiagnosis (PD). ALA is frequently administered topically or systemically topically or systemically for PDT or PD of several tumours. PPIX accumulation is greater in certain tumoural cell, due to the reduced activity of Ferrochelatase and relative increase of Deaminase. Early events: In 1975, Batlle et al. reported increased porphyrins synthesis from ALA in soybean callus, a highly dividing plant tissue, prevention of growth and finally death of the tissue. In 1987, Malik and Lugacy also reported destruction of erythroleukaemic dells by photoinactivation of endogenously formed porphyrins from ALA. In 1989 and years after, the group of Buenos Aires, using different explants of mice tissues, including mammary tumours, found that porphyrins synthesis increased with time and ALA concentrations, mainly in tumours. The first in vitro studies were reported in mammalian cells by Rebeiz et al and in an animal model developed in Buenos Aires, the first in vivo assays in colon, liver, stomach, subcutaneous mammary adenocarcinoma, endometrium and the first clinical studies in skin, colon and PD in neoplasic urothelial lesions, will be recalled. The mechanism of ALA transport in yeast will be considered. The approval of ALA for PDT in actinic keratoses and the present clinical PDT applications of ALA will be discussed. The use of more lipophilic derivatives of ALA, such as different ALA-derivatives, including the novel dendrimers synthesized in UK, as well as ALA esters, Methyl-ALA and Hexyl-ALA, in dermatology and PD and PDT in bladder cancer, will be recalled, also a reference to the approval of Metvix and Hexvix for PDT, since 1991 until March 2006, will be made. We will briefly talk about the different mechanisms of uptake of ALA and ALA derivatives in eukaryotic cells and the regulation fo porphyrins synthesis from these pro-drugs