Spectroscopic detection of oral and skin tissue transformation in a model for squamous cell carcinoma: autofluorescence versus systemic aminolevulinic acid-induced fluorescence

In recent years, applications of fluorescence spectroscopy to detect premalignant and malignant changes in various types of tissue has been proposed. The development of a safe and specific fluorescent agent that could enhance the spectroscopic contrast between normal and malignant tissue is highly desired. We explore the potential application of 5-aminolevulinic acid (ALA), a precursor of the endogenous fluorophore protoporphyrin IX (PpIX), to enhance fluorescence detection sensitivity with respect to the early identification of premalignant and malignant lesions. Using a hamster model for squamous cell carcinoma, the autofluorescence and ALA-induced fluorescence of the buccal mucosa and the external cheek skin were measured during tissue transformation. The measurements were analyzed using the ratio of PpIX-specific (632 nm) to PpIX-nonspecific fluorescence (595 nm)-defined as the red/orange ratio - and were correlated, to histopathologic assessment of lesion progression, During transformation of buccal mucosa from normal to premalignant to malignant lesion, a significant increase in both autofluorescence and ALA-induced fluorescence of tissue was observed. In contrast, in skin, tissue transformation was accompanied by a significant increase in ALA-induced fluorescence but not in autofluorescence. The fluorescence measurements correlated well with histopathological assessment of tumor development. Furthermore, at various stages of lesion development, an increase was found in the ability of transformed tissue to produce more PpIX at a faster rate as compared with normal tissue. In vivo measurement of autofluorescence may offer a promising technique for early detection of premalignant and malignant oral lesions. For skin, however, the sensitivity of this technique is inadequate. In this case, fluorescence sensitivity could be significantly enhanced by utilizing a low dose of ALA as a spectroscopic contrast agent to enhance tissue fluorescence, especially for early detection of tissue transformation.