Agents used in photodynamic therapy

First generation photosensitizers are based on haematoporphyrin (Hp) and haematoporphyrin derivative (HpD), the latter being a complex mixture of products based on the porphyrin structure. Photofrin is a preparation in which the monomers and unstable components of HpD have been substantially reduced, though it remains a mixture of porphyrin oligomers with peripheral-hydroxyl and -vinyl substituents and cannot be treated as a single compound in, for example, pharmacokinetic studies. Whilst Photofrin has been used with good effect in a variety of clinical trials, it is associated with various disadvantages as a photosensitizer; the second generation photosensitizers grew out of attempts to overcome these problems with Photofrin. Several chlorins which show increased absorbance of light further in the red, and hence enhance the tissue penetration of light, have been proposed for PDT; these include NPe6, and meta-tetrahydroxyphenyl chlorin (m-THPC, temoporfin, Foscan(TM)). Other second generation sensitizers are purpurins (SnET2), benzoporphyrins, phthalocyanines, texaphyrins, and aminolaevulinic acid, the latter being a naturally occurring amino acid and acting as a prodrug (it is transformed into protoporphyrin). It is concluded that the future role of PDT depends upon the development of photosensitizers that are safe, effective and readily formulated; they should also clear rapidly from the skin, so as to minimize the necessity for patients being protected from sunlight for an extended period after a PDT session.