Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer
Open accessAbstract
BACKGROUND: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides selective uptake and conversion of ALA into protoporphyrin IX (PpIX) in actinic keratosis and squamous cell carcinoma, yet large response variations in effect are common between individuals. The aim of this study was to compare pre-treatment strategies that increase the therapeutic effect, including fractionated light delivery during PDT (fPDT) and use of iron chelator desferrioxamine (DFO), separately and combined. METHODS: Optical measurements of fluorescence were used to quantify PpIX produced, and the total amount of PpIX photobleached as an implicit measure of the photodynamic dose. In addition, measurements of white light reflectance were used to quantify changes in vascular physiology throughout the PDT treatment. RESULTS: fPDT produced both a replenishment of PpIX and vascular re-oxygenation during a 2 h dark interval between the first and second PDT light fractions. The absolute photodynamic dose was increased 57% by fPDT, DFO and their combination, as compared with PDT group (from 0.7 to 1.1). Despite that light fractionation increased oedema and scab formation during the week after treatment, no significant difference in long-term survival has been observed between treatment groups. However, outcomes stratified on the basis of measured photodynamic dose showed a significant difference in long-term survival. CONCLUSIONS: The assessment of implicit photodynamic dose was a more significant predictor of efficacy for ALA-PDT skin cancer treatments than prescription of an enhanced treatment strategy, likely because of high individual variation in response between subjects.
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DFO significantly enhances ALA-PpIX fluorescence in glioblastoma and skin cancer animal models, although its effect on enhancing ALA-PDT in the skin tumor model is not statistically significant.
“Furthermore, it significantly enhances ALA-PpIX fluorescence in glioblastoma [89] and skin cancer [69] animal models, although its effect on enhancing ALA-PDT in the skin tumor model is not statistically significant.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [69]
More PpIX production and better tissue oxygenation occurring during the 2 h period between two illuminations likely increase tumor cell sensitivity to the second treatment.
“Although the detailed mechanism underlying increased response to double-illumination PDT remains unknown, more PpIX production and better tissue oxygenation occurring during the 2 h period between two illuminations likely increase tumor cell sensitivity to the second treatment [68,69].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [69]
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- Authors
- de Souza, A. L. R., Marra, K., Gunn, J., Samkoe, K. S., Kanick, S. C., Davis, S. C., Chapman, M. S., Maytin, E. V., Hasan, T., & Pogue, B. W.
- Affiliations
- Dartmouth College (US)
- Cleveland Clinic (US)
- Harvard University (US)
- Corresponding author
- Pogue, Brian W
- ORCID
- Venue
- British Journal of Cancer
- Published
- 2016-08-30
- Volume
- 115
- Issue
- 7
- Pages
- 805-813
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC5046214
- OpenAlex
- W2514227379
- Cited by
- 51
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 2 · 2018: 7 · 2017: 5 · 2016: 2
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BEX 1376/14-4)
- National Institutes of Health (CA084203)
- National Cancer Institute (P01CA084203)
- 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, 5-aminolevulinic acid, protoporphyrin IX, deferoxamine, iron chelation, actinic keratosis, squamous cell carcinoma, skin cancer, treatment response variability, long-term survival
- MeSH terms
- Aminolevulinic Acid, Animals, Carcinoma, Squamous Cell, Deferoxamine, Dose-Response Relationship, Radiation, Female, Heme, Humans, Lighting, Mice, Nude, Photochemotherapy, Protoporphyrins, Random Allocation, Skin Neoplasms, Siderophores, Photosensitizing Agents, Dose Fractionation, Radiation, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Mice, Lasers, Semiconductor
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