4 Following this there is also rapid systemic clearance of ALA-induced PpIX, within 24 hours.Īminolevulinic acid and its methylester, methyl aminolevulinate (MAL), are second-generation photosensitisers. Administration of sufficient ALA results in a rapid elevation (for a few hours) of PpIX levels, meaning that illumination can take place.
Although ALA has no intrinsic photosensitising properties, it is metabolised to produce PpIX (the active agent in ALA–PDT). An example is aminolevulinic acid (ALA), a naturally occurring intermediate in the haem biosynthetic pathway, and precursor of the photosensitising agent protoporphyrin IX (PpIX). These can be exploited to naturally generate therapeutic levels of photosensitiser. 3Īn alternative approach to introducing the photosensitiser to the target tissue involves making use of biomolecules produced by the body.
W D GANN PETER PALASKAS SKIN
Persistent levels will typically last for many weeks, causing photosensitivity of the skin (sunburn-like effects), unless patients avoid bright light. The second is the time taken for photosensitiser concentration to fall below clinically active levels.
One is the time taken (typically 48 hours) for tissues to accumulate sufficient levels of photosensitiser to allow the next stage of the PDT process to occur (illumination). There are two major drawbacks of using Ps or HpD. Ps and HpD are first-generation photosensitisers.
Its purified fraction is known as porfimer sodium (Ps). Many photosensitisers are derivatives of haematoporphyrin the first photosensitiser used clinically in PDT was haematoporphyrin derivative (HpD). Haemoglobin (which transports oxygen in the blood) and chlorophyll (an essential component of photosynthesis) molecules contain heterocyclic ring structures, known as porphyrins. PDT has also been used to treat age-related macular degeneration, cardiovascular disease, psoriasis, acne vulgaris and viral warts. Randomised controlled trials (RCTs) of PDT in patients with malignant and pre-malignant conditions began in earnest in the 1990s. 1 However, despite this early knowledge of the basic principles, it was not until the 1980s that PDT (which was then also often known as ‘photoradiation therapy’) developed to a level where it was used – to any significant extent – in both clinical research and practice. The photodynamic effect was discovered by chance over 100 years ago, followed shortly after by early pioneering work on PDT in Europe. This technique, known as photodynamic diagnosis (PDD), may be used alongside PDT. Some of the light absorbed by photosensitisers is re-emitted at a different wavelength, a process known as fluorescence this can be used as a means of detecting the presence and location of tumours. The photochemical reaction resulting from excitation of the photosensitiser produces singlet oxygen, which destroys cells (by reacting with, and damaging, cell organelles and biomolecules important to cell function). A period of time is required to permit photosensitiser uptake (ranging from a few minutes up to several days), after which light is directed at the area to be treated. Photosensitisers can be administered systemically or topically, which targeted cells then preferentially absorb. Photodynamic therapy (PDT) is the use of a light-sensitive drug (a photosensitiser), in combination with light of a visible wavelength, to destroy target cells (e.g. Chapter 1 General background Basics of photodynamic therapy