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Journal of Biomedical Optics

Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo
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Paper Abstract

As part of an ongoing program to develop two-photon (2-γ)photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

Paper Details

Date Published: 1 November 2009
PDF: 14 pages
J. Biomed. Opt. 14(6) 064006 doi: 10.1117/1.3262521
Published in: Journal of Biomedical Optics Volume 14, Issue 6
Show Author Affiliations
Mamta Khurana, Ontario Cancer Institute (Central African Republic)
Eduardo Hiroyuki Moriyama, Ontario Cancer Institute (Canada)
Adrian Mariampillai, Univ. of Toronto (Canada)
Kimberley S. Samkoe, Dartmouth College (United States)
David Cramb, Univ. of Calgary (Canada)
Brian C. Wilson, Ontario Cancer Institute (Canada)

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