Light and drug dosimetry considerations in porphyrin precursor–based photodynamic therapy
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- Fysisk institutt [3667]
Abstract
This thesis concerns light and drug dosimetry for photodynamic cancer treatment – a treatment modality where a photosensitizer uses the energy of light to damage biological matter. Porphyrin precursors were used as prodrugs which are synthesized into photosensitizers inside cells. Human subjects were studied as a part of developing a treatment for non-melanotic skin cancer. A 3-hour application of a topical cream photosensitized the tumor tissue with good selectivity versus normal skin, which suffered only mild phototoxic reactions after light exposure. Longer application times increased the photosensitizer content mainly in normal skin and superficial layers of the tumors. Light exposure using a filtered halogen lamp was found to be as efficient as a laser. A rat model was used to explore treatment of malignant brain tumors using systemic drug application. The intracranial light and photosensitizer distributions were mapped in detail. Treatment with low light dose rates was far more effective than with high dose rates. Significant tumor damage could be achieved with low dose rates, but the experiments suggested insufficient photosensitization of the tumor cells invading normal brain tissue.List of papers
I. Soler A.M., Angell-Petersen E., Warloe T., Tausjø J., Steen H.B., Moan J. and Giercksky K.E. (2000): Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Photochemistry and Photobiology 71: 724–729. The paper is not available in DUO. The published version is available at: https://doi.org/10.1562/0031-8655(2000)071<0724:PTOSBC>2.0.CO;2 |
II. Angell-Petersen E., Sørensen R., Warloe T., Soler A.M., Moan J., Peng Q. and Giercksky K.E. (2006): Porphyrin formation in actinic keratosis and basal cell carcinoma after topical application of methyl 5-aminolevulinate. Journal of Investigative Dermatology 126: 265–271 Journal of Investigative Dermatology 2006 126: 265–271. The paper is not available in DUO. The published version is available at: https://doi.org/10.1038/sj.jid.5700048 |
III. Angell-Petersen E., Christensen C., Müller C.R. and Warloe T. (2007): Phototoxic reaction and porphyrin fluorescence in skin after topical application of methyl aminolevulinate. British Journal of Dermatology 156: 301–307. The paper is not available in DUO. The published version is available at: https://doi.org/10.1111/j.1365-2133.2006.07638.x |
IV. Angell-Petersen E., Hirschberg H. and Madsen S.J. (2007): Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy. Journal of Biomedical Optics 12: 014003-1–014003-9. The paper is not available in DUO. The published version is available at: https://doi.org/10.1117/1.2709882 |
V. Angell-Petersen E., Spetalen S., Madsen S.J., Sun C.H., Peng Q., Carper S.W., Sioud M. and Hirschberg H. (2006): Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model. Journal of Neurosurgery 104: 109–117. The paper is not available in DUO. The published version is available at: https://doi.org/10.3171/jns.2006.104.1.109 |
VI. Madsen S.J., Angell-Petersen E., Spetalen S., Carper S.W., Ziegler S.A. and Hirschberg H. (2006): Photodynamic therapy of newly implanted glioma cells in the rat brain. Lasers in Surgery and Medicine 38: 540–548. The paper is not available in DUO. The published version is available at: https://doi.org/10.1002/lsm.20274 |