title: Photodynamic therapy enhances liposomal doxorubicin distribution in tumors during isolated perfusion of rodent lungs.
abstract: BACKGROUND
  Photodynamic therapy (PDT) at low drug-light conditions can enhance the transport of intravenously injected macromolecular therapeutics through the tumor vasculature. Here we determined the impact of PDT on the distribution of liposomal doxorubicin (Liporubicin™) administered by isolated lung perfusion (ILP) in sarcomas grown on rodent lungs.
  
  
  METHODS
  A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the left lung of Fischer rats. Treatment schemes consisted in ILP alone (400 μg of Liporubicin), low-dose (0.0625 mg/kg Visudyne®, 10 J/cm(2) and 35 mW/cm(2)) and high-dose left lung PDT (0.125 mg/kg Visudyne, 10 J/cm(2) and 35 mW/cm(2)) followed by ILP (400 μg of Liporubicin). The uptake and distribution of Liporubicin in tumor and lung tissues were determined by high-performance liquid chromatography and fluorescence microscopy in each group.
  
  
  RESULTS
  Low-dose PDT significantly improved the distribution of Liporubicin in tumors compared to high-dose PDT (p < 0.05) and ILP alone (p < 0.05). However, both PDT pretreatments did not result in a higher overall drug uptake in tumors or a higher tumor-to-lung drug ratio compared to ILP alone.
  
  
  CONCLUSIONS
  Intraoperative low-dose Visudyne-mediated PDT enhances liposomal doxorubicin distribution administered by ILP in sarcomas grown on rodent lungs which is predicted to improve tumor control by ILP.
authors: Division of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: C
authors: C
authors: Cheng
authors: Y
authors: Y
authors: Wang
authors: A
authors: A
authors: Haouala
authors: E
authors: E
authors: Debefve
authors: S
authors: S
authors: Andrejevic Blant
authors: T
authors: T
authors: Krueger
authors: M
authors: M
authors: Gonzalez
authors: J-P
authors: JP
authors: Ballini
authors: S
authors: S
authors: Peters
authors: L
authors: L
authors: Decosterd
authors: H
authors: H
authors: van den Bergh
authors: H-B
authors: HB
authors: Ris
authors: J Y
authors: JY
authors: Perentes
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D008081:Liposomes / Q000008:administration & dosage; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D010477:Perfusion; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D000077362:Verteporfin
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D004317:Doxorubicin