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
Photochemistry and Photobiology 2007 71: 724–729
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
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
British Journal of Dermatology 2007 156: 301–307
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
Journal of Biomedical Optics 2007 12: 014003-1–014003-9
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
Journal of Neurosurgery 2006 104: 109–117
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.
Lasers in Surgery and Medicine 2006 38: 540–548