title: Antegrade versus retrograde isolated lung perfusion: doxorubicin uptake and distribution in a sarcoma model.
abstract: BACKGROUND
  Antegrade and retrograde doxorubicin-based isolated lung perfusions were compared in rodents bearing a sarcomatous tumor in the perfused lung. Inasmuch as these tumors derive their vascularization from the bronchial artery system, we hypothesized that retrograde isolated lung perfusion through the pulmonary vein might result in an improved tumor drug uptake.
  
  
  METHODS
  Single-pass antegrade (n = 9) and retrograde (n = 9) isolated left lung perfusions were performed with 100 microg of doxorubicin in Fischer rats 10 days after subpleural tumor cell injection. The perfusion, washout, and recirculation times were 20, 10, and 60 minutes, respectively, followed by harvesting of the lung. The doxorubicin concentration and compartmental distribution in the tumor and in normal parenchyma of each perfused lung were measured by high-pressure liquid chromatography (6 animals of each group) and fluorescence microscopy (3 animals of each group).
  
  
  RESULTS
  Doxorubicin concentration and pattern of doxorubicin-based fluorescence signaling were comparable for both perfusion techniques in normal lung tissue. Antegrade and retrograde isolated lung perfusion resulted in similar tumor drug uptake, which was lower than in normal lung parenchyma, and in weak and sporadic fluorescence signaling emerging from the tumor periphery and from blood vessels situated within the tumor tissue.
  
  
  CONCLUSIONS
  Retrograde isolated lung perfusion did not confer a better doxorubicin uptake in the tumor as compared with antegrade lung perfusion despite the fact that the tumor vascularization in this model is based on the bronchial artery circulation.
authors.affiliation: Division of Thoracic Surgery, Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland. thorsten.krueger@chuv.ch
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krueger
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuemmerle
authors.forename: Snezana
authors.initials: S
authors.lastname: Andrejevic-Blant
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.forename: Youmin
authors.initials: Y
authors.lastname: Pan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ballini
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Laurent Arthur
authors.initials: LA
authors.lastname: Decosterd
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Hans-Beat
authors.initials: HB
authors.lastname: Ris
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin