title: Preclinical in vivo evaluation of NPe6-mediated photodynamic therapy on normal vasculature.
abstract: OBJECTIVE
  Current treatments of port-wine stain birthmarks typically involve use of a pulsed dye laser (PDL) combined with cooling of the skin. Currently, PDL therapy protocols result in varied success, as some patients experience complete blanching, while others do not. Over the past decade, we have studied the use of photodynamic therapy (PDT) as either a replacement or adjuvant treatment option to photocoagulate both small and large vasculature. The objective of the current study was to evaluate a PDT protocol that involves use of an alternate intravascular photosensitizer mono-L-aspartylchlorin-e6 (NPe6) activated by an array of low-cost light emitting diodes.
  
  
  METHODS
  To monitor the microvasculature, a dorsal window chamber model was installed on 22 adult male mice. The light source consisted of a custom-built LED array that emitted 10 W at a center wavelength of 664 nm (FWHM = 20 nm). The light source was positioned at a fixed distance from the window chamber to achieve a fixed irradiance of 127 mW/cm(2). A retroorbital injection of NPe6 (5 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose-response experimental design to evaluate the efficacy of NPe6-mediated PDT.
  
  
  RESULTS
  We observed three general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed an acute decrease in blood flow followed by gradual restoration of blood flow over the 7-day monitoring period; and (3) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period. Dose-response analysis enabled identification of 85 J/cm(2) as a characteristic radiant exposure required to achieve persistent vascular shutdown at Day 7 following PDT.
  
  
  CONCLUSIONS
  The experimental data suggest that NPe6-mediated PDT can achieve persistent vascular shutdown of normal microvasculature.
authors.affiliation: Beckman Laser Institute and Medical Clinic, Department of Surgery, University of California, Irvine, California 92612, USA.
authors.forename: Wesley J
authors.initials: WJ
authors.lastname: Moy
authors.forename: Shreyas J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Ben S
authors.initials: BS
authors.lastname: Lertsakdadet
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Arora
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Nielsen
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Bernard
authors.initials: B
authors.lastname: Choi
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D008297:Male; D051379:Mice; D055806:Microvessels / Q000187:drug effects* / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000528:radiation effects; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin