title: 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.
  
  
  CONCLUSIONS
  Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.
authors.affiliation: Department of Respiratory Medicine, Sohag Faculty of Medicine, Sohag University, Sohag 82524, Egypt.
authors.forename: Abdellah Hamed Khalil
authors.initials: AH
authors.lastname: Ali
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takizawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toba
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kenzaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D005453:Fluorescence; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism*; D012680:Sensitivity and Specificity; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX