DETECTION OF EARLY STAGES OF CARCINOGENESIS IN ADENOMAS OF MURINE LUNG BY 5-AMINOLEVULINIC ACID-INDUCED PROTOPORPHYRIN-IX FLUORESCENCE

Administration of the heme precursor 5-aminolevulinic acid (ALA) leads to the selective accumulation of the photosensitizer protoporphyrin I X (PpIX) in certain types of normal and abnormal tissues, This phenome non has been exploited clinically for detection and treatment of a var iety of malignant and nonmalignant lesions. The present preclinical st udy examined the specificity of ALA-induced porphyrin fluorescence in chemically induced murine lung tumors in vivo. During the early stages of tumorigenesis, ALA-induced PpIX fluorescence developed in hyperpla stic tissues in the lung and later in early lung tumor foci, In early tumor foci, maximum PpIX fluorescence occurred 2 h after the administr ation of ALA and returned to background levels after 4 h, There was ap proximately a 20-fold difference in PpIX fluorescence intensity betwee n tumor foci and the adjacent normal tissue, The specificity of ALA-in duced fluorescence for hyperplastic tissues and benign tumors in lung during tumorigenesis suggests a possible use for this fluorochrome in the detection of premalignant alterations in the lung by fluorescence endoscopy, Two non-small cell lung cancer cell lines developed ALA-ind uced PpIX fluorescence in vitro. These lines exhibited a light-dose-de pendent phototoxic response to ALA photodynamic therapy (PDT) in vitro . Because PpIX is a clinically effective photosensitizer for a wide va riety of malignancies, these results support the possible use of ALA-i nduced PpIX PDT for lung cancer.