Aminolaevulinic Acid ALA

ALA is a metabolic precursor in the biosynthesis of hemotoporphyrin, which generates endogenously an effective PDT sensitizer protoporphyrin IX, as shown in Structure 12.4. It thus provides an attractive alternative to the administration of an exogenous photosensitizer. Even though ALA can be endogenously generated from glycine and succinyl CoA, exogenous adm inistration of ALA is chosen for a controlled buildup of protoporphyrin IX (PplX). The advantages offered by ALA-induced PplX over Photofrin® are:

• Ability to reach optimum therapeutic ratio in 4-6 hours

• Rapid systemic clearance of the photosensitizer within 24 hours, thus not only eliminating prolonged skin photosensitivity, but also allowing repeated treatment every 24 hours

• Accurate analysis of sensitizer levels by in situ monitoring of its fluorescence

PplX has a molar extinction coefficient of only <5000M-1cm-1 at 635 nm. It undergoes photobleaching. ALA can be administered both systemically and topically. However, for local treatment of superficial skin lesions, it is often used in the form of a cream for topical application. Another limitation of ALA stems from its hydrophilic nature, which restricts its penetration through the keratinous lesion of normal skin. For this reason, lipophilic ALA esters may be preferable because they can penetrate cells more readily. ALA-induced PDT application has recently been accepted for the clinical treatment of actinic keratosis (Sharman et al., 1999).

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