Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma
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Purpose Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. Combining iron chelators with MAL has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This paper investigates this method of enhancement both in vitro and for the first time clinically for the treatment of nodular basal cell carcinoma (BCC). Methods Enhancement of MAL-induced PpIX accumulation by the iron chelator CP94 was quantified fluorometrically in human cultured cells (including three dermatological cell types). An open, dose-escalating, pilot study was then conducted in patients with nodular BCC, to determine the safety of this pharmacological modification. Results Large enhancements in PpIX accumulation were observed in the cultured cells when co-incubated with the iron chelator CP94. Clinically the addition of CP94 was found to be feasible and safe. In addition greater reductions in tumor depth were observed in the CP94 co-incubated tumors. Conclusion Iron chelation by CP94 is an effective enhancer of MAL-induced PpIX accumulation in vitro. This method of enhancement was safely applied to a clinical PDT protocol with no unexpected adverse effects reported. Although the clinical investigation was only intended to be a small pilot to assess safety, enhancements in tumor clearance were observed both clinically and histologically when CP94 was included in the photosensitizing cream.
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A small pilot clinical trial has demonstrated the safety and efficacy of combining MAL and CP94 for BCC treatment.
“Moreover, a small pilot clinical trial has demonstrated the safety and efficacy of combining MAL and CP94 for BCC treatment [98].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [98]
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- Authors
- Pye, A., Campbell, S., & Curnow, A.
- Affiliations
- Royal Cornwall Hospital (GB)
- Corresponding author
- Pye, Andrew
- ORCID
- Curnow, Alison
- Venue
- Journal of Cancer Research and Clinical Oncology
- Published
- 2008-02-01
- Volume
- 134
- Issue
- 8
- Pages
- 841-849
- ISSN
- 0084-5353 (ISSN-L)
- 0171-5216
- 1432-1335
- PMC
- PMC12160748
- OpenAlex
- W2058532864
- Cited by
- 32
- References
- 38
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 4 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Cancer Research and Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- Menzies Centre for Australian Studies, King's College London, University of London
- 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
- methyl aminolevulinate, photodynamic therapy, iron chelation, protoporphyrin IX, photosensitizer accumulation, nodular basal cell carcinoma, treatment safety, dose escalation
- MeSH terms
- Aged, Aged, 80 and over, Aminolevulinic Acid, Carcinoma, Basal Cell, Basal Cell Carcinoma, Humans, Iron Chelating Agents, Middle Aged, Photochemotherapy, Pilot Projects, Protoporphyrins, Pyridones, Skin Neoplasms, Photosensitizing Agents, Cell Line, Tumor, In Vitro Techniques
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