title: Microscopic analysis of the localization of two chlorin-based photosensitizers in OSC19 tumors in the mouse oral cavity.
abstract: OBJECTIVE
  The effect of photodynamic therapy (PDT) is dependent on the localization of photosensitizer in the treatment volume at the time of illumination. Investigation of photosensitizer pharmacokinetics in and around the treatment volume aids in determining the optimal drug light interval for PDT.
  
  
  METHODS
  In this paper we have investigated the distribution of the photosensitizers chlorin e6 and Bremachlorin in the oral squamous cell carcinoma cell-line OSC19-Luc-Gfp in a tongue tumor, tumor boundary, invasive tumor boundary, and normal tongue tissue by the use of confocal microscopy of frozen sections. Tongues were harvested at t = [3, 4.5, 6, 24, 48] hours after injection.
  
  
  RESULTS
  Both photosensitizers showed a decreasing fluorescence with increasing incubation time, and at all time points higher fluorescence was measured in tumor boundary than in tumor itself. For short incubation times, a higher fluorescence intensity was observed in the invasive tumor border and normal tissue compared to tumor tissue. Bremachlorin showed a small increase in tumor to normal ratio at 24 and 48 hours incubation time. Ce6 was undetectable at 48 hours. We did not find a correlation between photosensitizer localization and the presence of vasculature.
  
  
  CONCLUSIONS
  The modest tumor/tumor boundary to normal selectivity of between 1.2 and 2.5 exhibited by Bremachlorin 24 and 48 hours after administration may allow selective targeting of tongue tumors. Further studies investigating the relationship between Bremachlorin concentration and therapeutic efficacy PDT with long incubation times are warranted.
authors.affiliation: Department of Radiation Oncology, Center for Optical Diagnostics and Therapy, Postgraduate School Molecular Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: van Leeuwen-van Zaane
authors.forename: Pieter B A A
authors.initials: PB
authors.lastname: van Driel
authors.forename: Ute A
authors.initials: UA
authors.lastname: Gamm
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Snoeks
authors.forename: Henriëtte S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: Angelique
authors.initials: A
authors.lastname: van der Ploeg-van den Heuvel
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Henricus J C M
authors.initials: HJ
authors.lastname: Sterenborg
authors.forename: Arjen
authors.initials: A
authors.lastname: Amelink
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002735:Chlorophyllides; D004338:Drug Combinations; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011166:Porphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011897:Random Allocation; D014062:Tongue Neoplasms / Q000188:drug therapy*
chemical_list: D002735:Chlorophyllides; D004338:Drug Combinations; D017319:Photosensitizing Agents; D011166:Porphyrins; C000593241:bremachlorin; C549229:purpurin 5; C072905:chlorin p6; C062985:phytochlorin
keywords: chlorin; pharmacokinetics; photodynamic; quantitative