Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment

Abstract

Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…This can be explained by the increased uptake of MAL by the abnormal tissue. This occurs due to the cell changes in BCC as suggested by Martin et al [13]. Differences in the PpIX intensity may also be due to cell type from different tissues as observed by Inada et al [25].…”

“…This is possible because the photosensitizer molecules have higher affinity to cancer cells compared to normal cells. It has been shown widely in preclinical and clinical studies that PS fluorescence can be useful contrast for improved visualization of cancer region and help surgeons delineating tumor margins during surgical resections [11][12][13].By using 5-aminolevulinic acid (ALA) or the methyl aminolevulinate (MAL) as precursor of protoporphyrin IX (PpIX), it is possible to use fluorescence to quantify PpIX content at pre-and post-treatment [6,[14][15][16].…”

“…It has been shown that singlet oxygen is generated and PS is being consumed continuously during PDT (as called photobleaching process) and this consumption can be related to PDT outcome [13,17,18].Thus, one can get information about the PDT efficacy by quantifying the PpIX content before and after PDT. The observation of the accumulated PpIX fluorescence is crucial in quantifying photosensitizer content before PDT.…”

“…Based on previous studies [13,15,21], the aim of this work is to implement fluorescence imaging in a clinical protocol to improve the clinical outcome. In our multi-center clinical trial of PDT for skin cancer in Brazil, we have added three fluorescence measurements during PDT implementation.…”

Non-Invasive Treatment of Extensive Eyelid Cancerous Lesion by Photodynamic Therapy: A Case Report

“…The inflammatory process occurring after seven days following the first PDT session is observed in Figure 1, panel B, which is characterized by enhanced expression of pro-inflammatory cytokines and leukocyte infiltration [16]. Many studies on the efficacy of PDT on BCC have been published [4,17,18]. However, only few studies have reported on the topical application of PDT for the treatment of BCC of eyelid cancer [19,20].…”