Topical photodynamic therapy at low fluence rates - theory and practice

Photodynamic Therapy (PDT), with topically applied 5-aminolaevulinic acid a s the photosensitiser, is an effective treatment for various malignant and pre-malignant skin conditions. Several studies have shown the importance of fluence rate as well as fluence in the efficacy of PDT. We propose a measu re of PDT efficacy, Photodynamic Damage Dose (PDD), which uses the product of instantaneous fluence rates, photosensitiser concentrations and oxygen c oncentrations in its calculation. We derive a qualitative numerical model o f PDT and verify it by demonstrating an inverse fluence rate effect, increa sed efficacy of fractionated PDT, PDT induced hypoxia, and the dependence o f photobleaching on fluence rate under certain circumstances. We recommend that fluence, fluence rate and any fractionation regime used should be deta iled when reporting a trial as altering any of these has significant effect s on PDT efficacy. The model predicts that low fluence rate irradiations sh ould be as effective as high fluence rate irradiations if carried out over the same length of time. To test this we build a light emitting diode-based lamp (fluence rate of 7 mW cm(-2) at 635 nm) and used it to treat 32 super ficial basal cell carcinomas on 22 patients (30 min treatment time, fluence 12.6 J cm(-2)). The complete response rate at one year was 84%, which is c omparable to that achieved using higher fluence rate sources for similar tr eatment times. We conclude that this robust, inexpensive light source is ef fective for topical PDT. (C) 2001 Elsevier Science B.V. All rights reserved .