Photodynamic therapy with endogenous protoporphyrin
Abstract
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
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Exogenously applied ALA induces enhanced PpIX biosynthesis in tumor cells.
“The finding that enhanced PpIX biosynthesis can be induced by exogenously applied ALA in tumor cells has led to the use of ALA as a prodrug for PpIX-mediated photodynamic therapy (PDT) and photodiagnosis [5,6].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [6]
ALA in aqueous solution can penetrate through abnormal keratin but not normal keratin, and induces lesion-selective PpIX in the epidermis but not in the dermis.
“The finding made by Kennedy et al. that ALA in aqueous solution can penetrate through abnormal keratin but not normal keratin, and induces lesion-selective PpIX in the epidermis but not in the dermis led them to conduct the first clinical trial of ALA-PDT for actinic keratosis (AK) and superficial basal cell carcinomas (BCC) [6].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [6]
Since the first topical application of ALA in the treatment of basal cell carcinoma in 1990, the clinical use of ALA-PDT has continued to grow.
“Since the very first topical application of ALA in the treatment of basal cell carcinoma in 1990 [8], the clinical use of ALA-PDT is still growing.”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [8]
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- Authors
- Kennedy, J. C., Pottier, R. H., & Pross, D. C.
- Affiliations
- Queen's University (CA)
- Corresponding author
- Kennedy, J.C.
- Venue
- Journal of Photochemistry and Photobiology B: Biology
- Publisher
- Elsevier BV
- Published
- 1990-06
- Volume
- 6
- Issue
- 1-2
- Pages
- 143-148
- ISSN
- 1011-1344 (ISSN-L)
- OpenAlex
- W1506108633
- Cited by
- 1,509
- References
- 5
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 39 · 2023: 35 · 2022: 30 · 2021: 20 · 2020: 42 · 2019: 33 · 2018: 37 · 2017: 25 · 2016: 44 · 2015: 39 · 2014: 45 · 2013: 38 · 2012: 49
- FWCI
- 22.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Photochemistry and Photobiology B Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- photodynamic therapy, protoporphyrin IX, 5-aminolevulinic acid, heme biosynthesis, photosensitization, basal cell carcinoma, actinic keratosis, squamous cell carcinoma, topical application, cosmetic outcome
- MeSH terms
- Aminolevulinic Acid, Animals, Carcinoma, Basal Cell, Basal Cell Carcinoma, Carcinoma, Squamous Cell, Humans, Keratosis, Photochemotherapy, Prodrugs, Protoporphyrins, Radiation-Sensitizing Agents, Skin Neoplasms
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