Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents
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Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for photodynamic therapy (PDT) is limited by the maximum tolerated oral ALA dose (60 mg kg(-1)). This study investigates whether hydroxypyridinone iron-chelating agents can be used to enhance the tissue levels of PPIX, without increasing the administered dose of ALA. Quantitative charge-coupled device (CCD) fluorescence microscopy was employed to study PPIX fluorescence pharmacokinetics in the colon of normal Wistar rats. The iron chelator, CP94, when administered with ALA was found to produce double the PPIX fluorescence in the colonic mucosa, compared with the same dose of ALA given alone and to be more effective than the other iron chelator studied, CP20. Microspectrofluorimetric studies demonstrated that PPIX was the predominant porphyrin species present. PDT studies conducted on the colonic mucosa showed that the simultaneous administration of 100 mg kg(-1) CP94 i.v. and 50 mg kg(-1) ALA i.v. produced an area of necrosis three times larger than similar parameters without the iron-chelating agent with the same light dose. It is possible, therefore, to increase the amount of necrosis produced by ALA-induced PDT substantially, without increasing the administered dose of ALA, through the simultaneous administration of the iron-chelating agent, CP94.
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ALA in combination with CP94 induces significantly higher PpIX fluorescence than ALA alone in rat bladder urothelium and colonic mucosa.
“ALA in combination with CP94 induces significantly higher PpIX fluorescence than ALA alone in rat bladder urothelium [96] and colonic mucosa [97].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [97]
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- Authors
- Curnow, A., Mcllroy, B., Postle-Hacon, M., Porter, J., MacRobert, A., & Bown, S.
- Affiliations
- University College London (GB)
- ORCID
- Curnow, A
- Venue
- British Journal of Cancer
- Published
- 1998-11
- Volume
- 78
- Issue
- 10
- Pages
- 1278-1282
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2063198
- OpenAlex
- W2060574210
- Cited by
- 68
- References
- 8
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2019: 2 · 2018: 6 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- British Journal of Cancer (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by-nc-sa)
- Funders
- DUSA Pharmaceuticals
- 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 › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- 5-aminolevulinic acid, photodynamic therapy, protoporphyrin IX, colonic mucosa, necrosis, radiation enhancement
- MeSH terms
- Aminolevulinic Acid, Animals, Colon, Drug Interactions, Female, Iron Chelating Agents, Mucous Membrane, Necrosis, Photochemotherapy, Protoporphyrins, Pyridones, Rats, Wistar, Rats
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