title: Photodynamic therapy selectively enhances liposomal doxorubicin uptake in sarcoma tumors to rodent lungs.
abstract: BACKGROUND
  In specific conditions, photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial barrier in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We hypothesized that Visudyne(R)-mediated PDT could selectively increase liposomal doxorubicin (Liporubicin) uptake in sarcoma tumors to rodent lungs while sparing the normal surrounding tissue.
  
  
  METHODS
  Sarcoma tumors were generated subpleurally in the left lower lung lobe of 66 Fischer rats. Ten days following sarcoma implantation, tumors underwent different pre-treatment schemes: no PDT (controls), low-dose PDT (0.0625 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)) and high-dose PDT (0.125 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)). Liporubicin was then administered and allowed to circulate for 1, 3, or 6 hours. At the end of each treatment scheme, we assessed the uptake of Liporubicin in tumor and lung tissues by high-performance liquid chromatography and fluorescence microscopy.
  
  
  RESULTS
  In all PDT-treated groups, there was a significant enhancement of Liporubicin uptake in tumors compared to controls after 3 and 6 hours of drug circulation. In addition, Liporubicin distribution within the normal lung tissue was not affected by PDT. Thus, PDT pre-treatment significantly enhanced the ratio of tumor-to-lung drug uptake compared to controls. Finally, fluorescence microscopy revealed a well-detectable Liporubicin signaling throughout PDT-treated tumors but not in controls.
  
  
  CONCLUSIONS
  PDT is a tumor-specific enhancer of Liporubicin distribution in sarcoma lung tumors which may find a translation in clinics.
authors.affiliation: Division of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
authors.forename: Elodie
authors.initials: E
authors.lastname: Debefve
authors.forename: Amina
authors.initials: A
authors.lastname: Haouala
authors.forename: Snezana
authors.initials: S
authors.lastname: Andrejevic-Blant
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krueger
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ballini
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Laurent
authors.initials: L
authors.lastname: Decosterd
authors.forename: Hubert
authors.initials: H
authors.lastname: van den Bergh
authors.forename: Georges
authors.initials: G
authors.lastname: Wagnieres
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Perentes
authors.forename: Hans-Beat
authors.initials: HB
authors.lastname: Ris
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism*; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D010778:Photochemotherapy; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin