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

J Biomed Opt. 2009 Nov-Dec;14(6):064006. doi: 10.1117/1.3262521.

Abstract

As part of an ongoing program to develop two-photon (2-gamma) 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-gamma and 2-gamma activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-gamma 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-gamma PDT of AMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / drug effects*
  • Blood Vessels / physiology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Histocytochemistry
  • Macular Degeneration
  • Mice
  • Mice, Nude
  • Microscopy, Confocal
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / pharmacology*
  • Spectrometry, Fluorescence
  • Verteporfin

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin