title: Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels tumor vascular density.
abstract: BACKGROUND
  Visudyne®-mediated photodynamic therapy (PDT) at low drug/light conditions has shown to selectively enhance the uptake of liposomal doxorubicin in subpleural localized sarcoma tumors grown on rodent lungs without causing morphological alterations of the lung. The present experiments explore the impact of low-dose PDT on liposomal doxorubicin (Liporubicin™) uptake to different tumor types grown on rodent lungs.
  
  
  METHODS
  Three groups of Fischer rats underwent subpleural generation of sarcoma, mesothelioma, or adenocarcinoma tumors on the left lung. At least five animals of each group (sarcoma, n = 5; mesothelioma, n = 7; adenocarcinoma, n = 5) underwent intraoperative low-dose (10 J/cm(2) at 35 mW/cm(2) ) PDT with 0.0625 mg/kg Visudyne® of the tumor and the lower lobe. This was followed by intravenous (IV) administration of 400 µg Liporubicin™. After a circulation time of 60 min, the tumor-bearing lung was processed for HPLC analyses. At least five animals per group underwent the same procedure but without PDT (sarcoma, n = 5; mesothelioma, n = 5; adenocarcinoma, n = 6). Five untreated animals per group underwent CD31 immunostaining of their tumors with histomorphometrical assessment of the tumor vascularization.
  
  
  RESULTS
  Low-dose PDT significantly enhanced Liporubicin™ uptake to all tumor types (sarcoma, P = 0.0007; mesothelioma, P = 0.001; adenocarcinoma, P = 0.02) but not to normal lung tissue compared to IV drug administration alone. PDT led to a significantly increased ratio of tumor to lung tissue drug uptake for all three tumor types (P < 0.05). However, the tumor drug uptake varied between tumor types and paralleled tumor vascular density. The vascular density was significantly higher in sarcoma than in adenocarcinoma (P < 0.001) and mesothelioma (P < 0.001), whereas there was no significant difference between adenocarcinoma and mesothelioma.
  
  
  CONCLUSIONS
  Low-dose Visudyne®-mediated PDT selectively enhances the uptake of systemically administered liposomal doxorubicin in tumors without affecting the drug uptake to normal lung. However, drug uptake varied significantly between tumor types and paralleled tumor vascular density.
authors.affiliation: Division of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Wang
authors.forename: Michel
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
authors.forename: Amina
authors.initials: A
authors.lastname: Haouala
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krueger
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Laurent-Arthur
authors.initials: LA
authors.lastname: Decosterd
authors.forename: Hubert
authors.initials: H
authors.lastname: van den Bergh
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Perentes
authors.forename: Hans-Beat
authors.initials: HB
authors.lastname: Ris
authors.forename: Igor
authors.initials: I
authors.lastname: Letovanec
authors.forename: Elodie
authors.initials: E
authors.lastname: Debefve
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008081:Liposomes; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D008654:Mesothelioma / Q000098:blood supply / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011166:Porphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000098:blood supply / Q000188:drug therapy; D016896:Treatment Outcome; D000077362:Verteporfin
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D004317:Doxorubicin