Clinical uses of 5-aminolaevulinic acid in photodynamic treatment and photodetection of cancer: A review
Abstract
ALA-mediated Photodynamic Therapy (ALA-PDT) is one of the most promising fields in Photodynamic therapy (PDT) research for cancer treatment. 5-aminolaevulinic acid (ALA) is the prodrug of the photosensitiser Protoporphyrin IX (PpIX). After ALA administration, cells generate PpIX through the haem biosynthetic pathway. Although the exact reasons for ALA/PpIX selectivity are unknown, it is believed that due to the special regulation of haem enzymes, PpIX is accumulated in the tumours. Both ALA and its derivative ALA Methyl ester, are mainly used in dermatology. Besides, ALA-PDT has been employed for palliative and even curative treatment of endoscopically accessible tumours. Lung, oesophagus, gastric and bladder carcinomas, and also oral premalignant lesions, gynaecological intraepithelial neoplasias and Barrett's oesophagus are the conditions mostly treated with ALA-PDT. However, due to the limited penetration of ALA and light, non-dermatologic uses of ALA-PDT have not moved beyond phase I clinical trials. On the other hand, ALA-induced PpIX fluorescence is successfully employed for the Photodynamic Diagnosis (PDD) or assistance in cytoreductive surgery (Fluorescence-guided Resection, FGR). ALA has been approved for the FGR of high-grade gliomas and ALA Hexyl ester, for fluorescence cystoscopy in the diagnosis of bladder cancer. ALA-FGR is currently applied in brain, bladder, lung, colon cancers, etc. and ALA-PDD for oral premalignancies, gynaecological intraepithelial lesions and peritoneal metastases, among others. Besides, PDT can be applied concomitantly in the same diagnostic procedure. This review aimed to analyse the state of the art of clinical uses of ALA in the areas of treatment and detection in the non-dermatologic oncology fields.
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As therapeutic agents, ALA and its derivatives are commonly used for treating superficial skin lesions including actinic keratosis and basal cell carcinoma with high clearance rates.
“As therapeutic agents, they are commonly used for treating superficial skin lesions including actinic keratosis and basal cell carcinoma with high clearance rates.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
As fluorescence imaging probes, ALA and its derivatives reveal bladder tumors and gliomas that are invisible to surgeons and facilitate tumor resection with high accuracy and precision.
“As fluorescence imaging probes for tumor diagnosis, they are able to reveal bladder tumors and gliomas that are invisible to surgeons and facilitate tumor resection with high accuracy and precision.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
ALA and its derivatives have received worldwide approval as tumor diagnostic and therapeutic drugs.
“ALA and its derivatives have currently received worldwide approval as tumor diagnostic and therapeutic drugs (Table 1) [7].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
ALA-based drugs are playing important roles in managing some common human diseases including AK and BCC, and highly morbid diseases such as high-grade gliomas.
“They are playing important roles in managing some common human diseases including AK (the most common precancerous lesion) and BCC (the most common cancer), and highly morbid diseases such as high-grade gliomas (Figure 3).”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
Since the first approval in 1999, five ALA-based drugs have been approved by the U.S. FDA.
“Since the first approval in 1999, five ALA-based drugs have been approved by the U.S. FDA.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
These drugs are approved not only in the US but also in many other countries.
“These drugs are approved not only in the US but also in many other countries [7].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [7]
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Islam, R., Kotalík, K., Šubr, V., Gao, S., Zhou, J.-R., Yokomizo, K., Etrych, T., & Fang, J. Q. (2022) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2022.102636 · Cited by 5 · see citing works
Photosensitized Oxidation of Free and Peptide Tryptophan to N-Formylkynurenine
Farías, J. J., Dántola, M. L., & Thomas, A. H. (2024) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.4c00229 · Cited by 5 · see citing works
Calvo, G. H., Céspedes, M. A., Casas, A. G., Venosa, G. M. D., & Sáenz, D. A. (2022) · Nitric Oxide · doi:10.1016/j.niox.2022.06.006 · Cited by 5 · see citing works
Self-citationZhou, Y., Mo, M., Luo, D., Yang, Y., Hu, J., Ye, C., Lin, L., Xu, C., & Chen, W. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14071477 · Cited by 5 · see citing works
Lv, H., Suo, Y., Sun, Q., Fan, J., & Wang, Q. (2023) · Advances in Medical Sciences · doi:10.1016/j.advms.2023.03.001 · Cited by 5 · see citing works
- Authors
- Casas, A.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Casas, Adriana
- ORCID
- Casas, Adriana
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 490
- Pages
- 165-173
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W3034955339
- Cited by
- 164
- References
- 95
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 32 · 2023: 27 · 2022: 28 · 2021: 29 · 2020: 4
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- 5-aminolevulinic acid, photodynamic therapy, protoporphyrin IX, heme biosynthesis, photodynamic diagnosis, fluorescence-guided resection, fluorescence cystoscopy, oral potentially malignant disorders, Barrett's esophagus, bladder cancer, high-grade glioma, peritoneal carcinomatosis, tumor selectivity
- MeSH terms
- Aminolevulinic Acid, Animals, Humans, Neoplasms, Photochemotherapy, Photosensitizing Agents
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