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Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents
- Source :
- British Journal of Cancer, Scopus-Elsevier
- Publication Year :
- 1998
- Publisher :
- Nature Publishing Group|1, 1998.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Necrosis
Colon
Pyridones
medicine.medical_treatment
Protoporphyrins
Photodynamic therapy
Pharmacology
Iron Chelating Agents
chemistry.chemical_compound
Pharmacokinetics
Fluorescence microscope
medicine
Animals
Photosensitizer
Chelation
Drug Interactions
Rats, Wistar
Mucous Membrane
Protoporphyrin IX
Aminolevulinic Acid
Rats
Oncology
chemistry
Biochemistry
Photochemotherapy
Protoporphyrin
Female
medicine.symptom
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15321827 and 00070920
- Volume :
- 78
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....844318c16afca6e0f449a2759d5c2266