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Volume 23
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10.3390/ijms23126478
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Review

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges

by
Yoshinori Harada
1,*,
Yasutoshi Murayama
2,
Tetsuro Takamatsu
3,
Eigo Otsuji
2 and
Hideo Tanaka
1
1
Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto 602-8566, Japan
2
Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto 602-8566, Japan
3
Department of Medical Photonics, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto 602-8566, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(12), 6478; https://doi.org/10.3390/ijms23126478
Submission received: 2 May 2022 / Revised: 2 June 2022 / Accepted: 7 June 2022 / Published: 9 June 2022
(This article belongs to the Special Issue Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders)
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Abstract

5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.
Keywords: 5-aminolevulinic acid; protoporphyrin IX; tumor; photodynamic diagnosis 5-aminolevulinic acid; protoporphyrin IX; tumor; photodynamic diagnosis

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MDPI and ACS Style

Harada, Y.; Murayama, Y.; Takamatsu, T.; Otsuji, E.; Tanaka, H. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges. Int. J. Mol. Sci. 2022, 23, 6478. https://doi.org/10.3390/ijms23126478

AMA Style

Harada Y, Murayama Y, Takamatsu T, Otsuji E, Tanaka H. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges. International Journal of Molecular Sciences. 2022; 23(12):6478. https://doi.org/10.3390/ijms23126478

Chicago/Turabian Style

Harada, Yoshinori, Yasutoshi Murayama, Tetsuro Takamatsu, Eigo Otsuji, and Hideo Tanaka. 2022. "5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges" International Journal of Molecular Sciences 23, no. 12: 6478. https://doi.org/10.3390/ijms23126478

APA Style

Harada, Y., Murayama, Y., Takamatsu, T., Otsuji, E., & Tanaka, H. (2022). 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges. International Journal of Molecular Sciences, 23(12), 6478. https://doi.org/10.3390/ijms23126478

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