Wavelength Dependency of Photodynamic Effects After Sensitization with 5-Aminolevulinic Acid In Vitro and In Vivo

A promising new therapeutic modality for skin cancer, administration of the heme precursor 5-aminolevulinic acid followed by light irradiation, is known as photodynamic therapy. Photofrin, the only clinically approved sensitizer, has an absorption maximum at 630 nm, the wavelength used in most exper...

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Bibliographic Details
Published in:Journal of investigative dermatology 1995-11, Vol.105 (5), p.672-677
Main Authors: Szeimies, Rolf-Markus, Abels, Christoph, Fritsch, Clemens, Karrer, Sigrid, Stinbach, Pia, Bäumler, Wolfgang, Goerz, Günter, Goetz, Alwin E., Landthaler, Michael
Format: Article
Language:English
Subjects:
Aminolevulinic Acid - pharmacology
Animals
Cell Line - metabolism
Cell Survival - radiation effects
Cricetinae
dye laser
Humans
Keratinocytes - cytology
Keratinocytes - radiation effects
Light
Mesocricetus
Microscopy, Confocal
Neoplasm Transplantation
Photochemotherapy - methods
photodynamic therapy
Photosensitizing Agents - pharmacology
porphyrins
Protoporphyrins - biosynthesis
skin cancer
Tumor Cells, Cultured
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Summary:A promising new therapeutic modality for skin cancer, administration of the heme precursor 5-aminolevulinic acid followed by light irradiation, is known as photodynamic therapy. Photofrin, the only clinically approved sensitizer, has an absorption maximum at 630 nm, the wavelength used in most experimental and clinical trials with 5-aminolevulinic acid. We investigated photodynamic efficacy of irradiation with coherent light at wavelengths ranging from 622 to 649 nm in vitro and in vivo as well as the content and distribution of intracellular porphyrin after administration of 5-aminolevulinic acid. HaCaT immortalized human keratinocytes were sensitized with 30 μg/mI 5-aminolevulinic acid for 24 h in vitro. By cell viability determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, the best cell-killing effects were observed after irradiation at 635 nm. Using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, we confirmed these results in vivo: tumor growth was markedly delayed in animals treated with 100 mg/kg 5-aminolevulinic acid intravenously and irradiated with coherent light at 635 nm as compared to animals irradiated at 630 nm. This photodynamic effect is probably mediated by large amounts of the photosensitizing porphyrin, protoporphyrin IX, localized in cell membranes as visualized by confocal laser scan microscopy and as determined by high pressure liquid chromatography in vitro. The results suggest that irradiation at 635 nm with a coherent light source is more effective than irradiation at 630 nm for photodynamic therapy with 5-aminolevulinic acid.
ISSN:0022-202X
1523-1747
DOI:10.1111/1523-1747.ep12324377