5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor

Abstract

Background: It is known that endogenously synthesized protoporphyrin IX (PpIX) following the administration of 5-aminolevulinic acid (5-ALA) is an effective photosensitizer for photodynamic diagnosis (PDD). We tested in vivo and in vitro susceptibility of human lung cancer and mesothelioma cells to photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) as a photosensitizer.

Methods: Human lung cancer cell lines A549, Ma44-3, FT821 and human mesothelioma cell lines MSTO-211H, NCI-H290, Y-MESO-14 were incubated with 0.03% 5-ALA for 4 h. After incubation, protoporphyrin IX (PpIX) fluorescence was detected using a fluorescence microscope. Pleural carcinosis was induced in severe combined immunodeficiency disease mice using the previous cell lines to test the efficacy of PDD in vivo. The mice were sacrificed 4 h after oral administration of 400 mg/kg of 5-ALA. We counted the visible tumors under white light then fluorescence light.

Results: In vitro, clear red fluorescence was observed in all cell lines. The mean fluorescence intensity was stronger in A549 and FT821 cells than Ma44-3 cells (165.59±26.49, 157.62±18.93 vs. 104.01±17.58). Also, MSTO-211H and NCI-H290 cells had stronger fluorescence intensity than Y-MESO-14 cells (142.51±26.85, 165.16±12.91 vs. 92.31±8.69). In vivo, the tumor detection rate of fluorescence diagnosis was 1.1-4.5 times higher than that of white light. The mean number of metastases detected by the PDD was significantly higher than that of white light for FT821 (p=0.004), Ma44-3 (p=0.006) and Y-MESO-14 cell lines (p=0.005), but not for A549, NCI-H290 and MSTO-211H cell lines. Small lesions were detected by fluorescence diagnosis even though the lesions were invisible macroscopically under white light.

Conclusion: Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.