Antegrade versus retrograde isolated lung perfusion: doxorubicin uptake and distribution in a sarcoma model.
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.
Krueger
Thorsten
T
Division of Thoracic Surgery, Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland. thorsten.krueger@chuv.ch
Kuemmerle
Andrea
A
Andrejevic-Blant
Snezana
S
Yan
Hua
H
Pan
Youmin
Y
Ballini
Jean-Pierre
JP
Klepetko
Walter
W
Decosterd
Laurent Arthur
LA
Stupp
Roger
R
Ris
Hans-Beat
HB
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
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin