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

Our plain-English summary of 5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor, by A.H. Ali, H. Takizawa, K. Kondo, et al (Lung Cancer, 2011).

The study

• Authors: A.H. Ali, H. Takizawa, K. Kondo, H. Matsuoka, H. Toba, Y. Nakagawa, K. Kenzaki, S. Sakiyama, S. Kakiuchi, Y. Sekido, S. Sone, A. Tangoku
• Journal: Lung Cancer
• Published: 2011;74(1):48-54
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This laboratory and animal study, from the University of Tokushima, Japan, tested whether 5-aminolevulinic acid (5-ALA), which makes tumor cells glow red under blue light, could help find tumors in the chest cavity. It did not study asbestos exposure. Three human lung cancer cell lines and three human mesothelioma cell lines were treated with 5-ALA in dishes. All six glowed clearly red, though brightness differed between cell lines. In a separate experiment, the same cell lines were injected into the chest cavity of immunodeficient mice, 10 per line, and grown into tumors for 1 to 3 weeks; some mice were lost because of massive chest fluid. The mice were then given 400 mg/kg of 5-ALA by mouth. Tumors were counted under white light, then under blue light. Blue light found more tumors for every cell line, with a detection rate 1.1 to 4.5 times higher. The difference was statistically significant only for one mesothelioma line (Y-MESO-14: 8.66 versus 14.33 tumors on average) and two lung cancer lines. Small lesions invisible under white light were detected. The authors concluded the results suggest possible clinical use for tumors in the pleural cavity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-line experiment combined with an animal (mouse) experiment
• Who was studied: Three human lung cancer cell lines (Ma44-3, squamous cell; A549, adenocarcinoma; FT821, large cell) and three human mesothelioma cell lines (MSTO-211H, Y-MESO-14, NCI-H290). In the animal experiment, cells from these lines were injected into the left pleural cavity of male severe combined immunodeficiency (SCID) mice, aged 6 weeks and weighing 20 to 25 g, with 10 mice per cell line. Tumors were allowed to grow for 1 to 3 weeks depending on the cell line. Mice were lost because of massive thoracic effusions: 1 in Ma44-3, 2 in MSTO-211H, 1 in Y-MESO-14, 5 in A549 and 2 in NCI-H290. The work was done at the University of Tokushima, Japan. Study dates are not given.
• Exposure: No asbestos exposure was studied. The substance tested was 5-aminolevulinic acid (5-ALA): 0.03% for 4 hours in cell culture, and 400 mg/kg body weight by mouth, given 4 hours before fluorescence diagnosis in mice. A preliminary dose of 100 mg/kg gave unclear fluorescence.
• Main results:
  • In cell culture, the mean fluorescence intensity of the lung cancer cell lines was 165.59 (SD 26.49) for A549, 157.62 (SD 18.93) for FT821 and 104.01 (SD 17.58) for Ma44-3.
  • In cell culture, the mean fluorescence intensity of the mesothelioma cell lines was 142.51 (SD 26.85) for MSTO-211H, 165.16 (SD 12.91) for NCI-H290 and 92.31 (SD 8.69) for Y-MESO-14.
  • In mice, the mean number of tumors found under fluorescence was higher than under white light for all six cell lines.
  • In mice, the tumor detection rate of fluorescence diagnosis was 1.1 to 4.5 times higher than that of white light.
  • Mean tumor foci, white light versus blue light, in the Y-MESO-14 (mesothelioma) group: 8.66 (SD 5.80) versus 14.33 (SD 8.83), p = 0.005.
  • Mean tumor foci, white light versus blue light, in the MSTO-211H (mesothelioma) group: 10.37 versus 14.37, p = 0.053 (not statistically significant).
  • Mean tumor foci, white light versus blue light, in the NCI-H290 (mesothelioma) group: 18.37 versus 20, p = 0.154 (not statistically significant).
  • Mean tumor foci, white light versus blue light, in the lung cancer groups: FT821 5.2 versus 23.5 (p = 0.004); Ma44-3 12.44 versus 19.22 (p = 0.006); A549 17.4 versus 20.4 (p = 0.247, not significant).
  • Small lesions that could not be seen under white light were identified only by their red fluorescence.
  • All biopsied lesions, whether seen by normal inspection or detected by fluorescence, were confirmed as cancer under the microscope.
  • Some large tumors did not fluoresce, although these were easily seen under white light.
• The authors' conclusion: The authors concluded that their results suggest the possibility of clinical use of fluorescence diagnosis for tumors inside the pleural cavity. They said the results confirm this possibility for locating mesothelioma implants in an animal model.
• Limitations the authors state:
  • Fluorescence diagnosis is limited to surface lesions, because the depth at which tumors can be detected depends on the wavelength of the light used, and blue light penetrates tissue poorly.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma.

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