Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo.
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.
Khurana
Mamta
M
University of Toronto, Division of Biophysics and Bioimaging, Department of Medical Biophysics, Ontario Cancer Institute, Toronto, Ontario M5G2M9, Canada.
Moriyama
Eduardo H
EH
Mariampillai
Adrian
A
Samkoe
Kimberley
K
Cramb
David
D
Wilson
Brian C
BC
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006651:Histocytochemistry; D008268:Macular Degeneration; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin