The effect of an iron chelating agent on protoporphyrin IX levels and phototoxicity in topical 5-aminolaevulinic acid photodynamic therapy
Abstract
BACKGROUND: In 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron. OBJECTIVES: To explore the potential of the iron chelator desferrioxamine (DFO) to enhance PpIX levels and phototoxicity in ALA-PDT. METHODS: A series of six doses of 2% ALA solution was iontophoresed into the healthy skin of each ventral forearm of 10 volunteers. One arm was pretreated with 20% DFO in aqueous cream, while the control arm received aqueous cream alone, for 16 h. At 5 h following iontophoresis, skin-surface PpIX fluorescence was measured, following which the forearms were simultaneously irradiated with 100 J cm-2 broadband red light. The phototoxic reaction was assessed at 24 h postirradiation as the minimal phototoxic dose (MPD) and with quantification of erythema. Next, eight patients with two superficial basal cell carcinomas or two plaques of Bowen's disease of similar appearance received 20% ALA topically to one lesion and 20% ALA with 20% DFO to the other, for 3 h. Skin-surface PpIX fluorescence was measured at 5 h, following which lesions were irradiated with 100 J cm-2 broadband red light. RESULTS: In healthy skin, PpIX fluorescence increased with increasing ALA dose at DFO-treated and untreated sites (P < 0.0005); PpIX fluorescence peak values were consistently higher in DFO-treated compared with control sites (P < 0.02). Erythema also correlated with ALA dose (P < 0.0005), but a significant difference between active and control sites occurred only at low ALA dose (P < 0.05). The median MPD appeared lower at the DFO-treated sites, at 6 mC vs. 12 mC (P = 0.06). In contrast, in lesional skin there was no consistent difference in PpIX fluorescence levels between those treated with and without DFO. CONCLUSIONS: While iron chelation augmented ALA-PDT phototoxicity in normal skin, this occurred only at low ALA dose. Addition of DFO does not appear to confer additional benefit in ALA-PDT of nonmelanoma skin cancers.
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EDTA does not increase PpIX production in a mouse tumor model and BCC patients after ALA administration, and DFO does not enhance PpIX fluorescence in skin cancer patients.
“Despite these promising results from many in vitro studies, EDTA does not increase PpIX production in a mouse tumor model [102] and BCC patients [103] after ALA administration, and DFO does not enhance PpIX fluorescence in skin cancer patients either [104].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [104]
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- Authors
- Choudry, K., Brooke, R. C. C., Farrar, W., & Rhodes, L. E.
- Affiliations
- Salford Royal Hospital (GB)
- Royal Liverpool University Hospital (GB)
- Corresponding author
- Rhodes, L.E.
- ORCID
- Rhodes, L.E.
- Venue
- British Journal of Dermatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-07
- Volume
- 149
- Issue
- 1
- Pages
- 124-130
- ISSN
- 0007-0963 (ISSN-L)
- 1365-2133
- OpenAlex
- W2018664136
- Cited by
- 65
- References
- 23
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Skin Foundation
- 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
- 5-aminolevulinic acid, photodynamic therapy, protoporphyrin IX, deferoxamine, iron chelation, phototoxicity, iontophoresis, basal cell carcinoma, Bowen's disease, erythema, topical photosensitizer, skin cancer treatment, minimal phototoxic dose, red light
- MeSH terms
- Administration, Cutaneous, Adult, Aged, Aged, 80 and over, Aminolevulinic Acid, Bowen's Disease, Carcinoma, Basal Cell, Basal Cell Carcinoma, Deferoxamine, Dose-Response Relationship, Drug, Drug Therapy, Combination, Erythema, Female, Fluorescence, Humans, Iontophoresis, Iron Chelating Agents, Male, Middle Aged, Photochemotherapy, Protoporphyrins, Skin Neoplasms
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