Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

Abstract

Abstract. Topical 5-aminolevulinic acid ͑ALA͒ is widely used in photodynamic therapy ͑PDT͒ of actinic keratoses ͑AK͒, a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX ͑PpIX͒ accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements ͑5 replicates͒ were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin. © 2010 Society of Photo-Optical Instrumentation Engineers.

Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

“…Excitation laser light of 405 nm wavelength was launched down a single 100-μm-diameter quartz optical fiber to the skin (Figure 4A), and the fluorescent light induced was collected by seven optical fibers surrounding the excitation fiber (Figure 4B), for measurement by a photodetector. Serial measurements taken every 30 min after ALA application revealed a linear rate of accumulation in all patients, with statistically significant PpIX levels reached in nearly 100% of patients by 2 h and thereby justifying the use of short-contact PDT in the clinic [49]. Moreover, the PpIX fluorescence amplitude was correlated with biological response, as measured by erythema within lesions (Figure 4C, D).…”

“…A more difficult question is whether the amount of PpIX production in neoplastic lesions can predict successful clinical outcome. In a clinical study using a fluorescence point dosimeter, Warren et al [49] asked whether PpIX-mediated fluorescence measurements are predictive of biological responses to ALA-PDT in squamous precancers (AK) in 20 patients. Excitation laser light of 405 nm wavelength was launched down a single 100-μm-diameter quartz optical fiber to the skin (Figure 4A), and the fluorescent light induced was collected by seven optical fibers surrounding the excitation fiber (Figure 4B), for measurement by a photodetector.…”

5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

“…The technology for measuring PpIX photosensitizer levels in the AK lesions and in surrounding normal skin, using noninvasive fluorescence monitoring, is available (Warren et al 33 , so that an effect of 5-FU on PpIX can be readily tested in clinical studies to establish proof-of-principle. …”

Fluorescence guided PDT for optimization of the outcome of skin cancer treatment

“…The photosensitizer is a molecule, which absorbs light at specific wavelengths, and once the light is absorbed, the molecule passes from the ground state to an excited state. From this excited metastable state, the molecule can transfer energy to other molecules, starting the photodynamic reaction, or the molecule returns to the ground state releasing energy as photons, a irradiative process known as fluorescence [1][2][3][4][5][6][7], which identifies the presence of the photo sensible molecules. While the photodynamic route takes to the killing of cell, the fluorescence is on mechanism for diagnostic.…”