Evaluation of angiogenesis using micro-computed tomography in a xenograft mouse model of lung cancer.
Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, through the jugular vein (in vivo application) or pulmonary artery (ex vivo application). In addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically with humanized monoclonal antibody (bevacizumab) against vascular endothelial growth factor. Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm(2)) were filled using the in vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore, bevacizumab-treated lung tumor-bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT. Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm(2)) was reduced after bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis, and this might be considered as an additional complementary tool for precise quantification of angiogenesis.
Savai
Rajkumar
R
Department of Hematology and Oncology, Justus-Liebig-University, Giessen, Germany. Savai.Rajkumar@innere.med.uni-giessen.de
Langheinrich
Alexander Claus
AC
Schermuly
Ralph Theo
RT
Pullamsetti
Soni Savai
SS
Dumitrascu
Rio
R
Traupe
Horst
H
Rau
Wigbert Stephan
WS
Seeger
Werner
W
Grimminger
Friedrich
F
Banat
Gamal Andre
GA
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008175:Lung Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009928:Organ Specificity / Q000187:drug effects; D014407:Tumor Cells, Cultured; D055114:X-Ray Microtomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab