5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models

• Published in: PloS one 2021-04, Vol.16 (4), p.e0249650-e0249650
• Main Authors: Sasaki, Makiko, Tanaka, Mamoru, Ichikawa, Hiroshi, Suzuki, Taketo, Nishie, Hirotada, Ozeki, Keiji, Shimura, Takaya, Kubota, Eiji, Tanida, Satoshi, Kataoka, Hiromi
• Format: Article
• Language: English
• Subjects: Aminolevulinic Acid; Animal sciences; Animals; Biology and Life Sciences; Brain cancer; Cell Line, Tumor; Computer programs; Diagnosis; Disease Models, Animal; Editing; Experiments; Female; Flow Cytometry - methods; Fluorescence; Gastroenterology; Gastrointestinal cancer; Gastrointestinal Stromal Tumors - diagnosis; Gastrointestinal Stromal Tumors - metabolism; Gastrointestinal system; Gastrointestinal tract; Glucose; Graduate schools; Graduate studies; Health services; Humans; Laboratory animals; Lasers; Levulinic Acids - metabolism; Localization; Medical diagnosis; Medical science; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Photochemotherapy - methods; Photosensitizing Agents - metabolism; Physical Sciences; Protoporphyrins - metabolism; Research and Analysis Methods; Software; Tumors; University graduates; Xenograft Model Antitumor Assays - methods; Xenografts; Xenotransplantation; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0249650

Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.