title: Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice.
abstract: The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.|Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming, 650500, Yunnan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.|IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Heuillard
authors.affiliation: Pathology Department, University Hospital of Strasbourg, 67000 Strasbourg, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lindner
authors.affiliation: Mouse Clinical Institute, 67400 Illkirch, France.
authors.forename: Ghina
authors.initials: G
authors.lastname: Bou About
authors.affiliation: Pôle Hépatodigestif, Unité Hépatologie, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.|Research Institute against Cancer of the Digestive System (IRCAD), 67000 Strasbourg, France.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ignat
authors.affiliation: University of Strasbourg, 67000 Strasbourg, France.|Functional Unit 6237, Preclinical Imaging, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.|National Center for Scientific Research (CNRS), ICube, MMB team, 67000 Strasbourg, France.|Medical Faculty, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dillenseger
authors.affiliation: University of Strasbourg, 67000 Strasbourg, France.|National Center for Scientific Research (CNRS), UMR 7199, 67400 Illkirch, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Anton
authors.affiliation: LLTech SAS, 75014 Paris, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Dalimier
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Gossé
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Gael
authors.initials: G
authors.lastname: Fouré
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Blindauer
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Giraudeau
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Saghire
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Bouhadjar
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Calligaro
authors.affiliation: Mouse Clinical Institute, 67400 Illkirch, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Sorg
authors.affiliation: University of Strasbourg, 67000 Strasbourg, France.|Functional Unit 6237, Preclinical Imaging, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.|National Center for Scientific Research (CNRS), ICube, MMB team, 67000 Strasbourg, France.|Medical Faculty, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Choquet
authors.affiliation: University of Strasbourg, 67000 Strasbourg, France.|National Center for Scientific Research (CNRS), UMR 7199, 67400 Illkirch, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Vandamme
authors.affiliation: French Blood Agency Bourgogne/Franche-Comté, 25000 Besançon, France.|INSERM, U 1098, 25000 Besançon, France.|Université de Franche-Comté, 25000 Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.|Pôle Hépatodigestif, Unité Hépatologie, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.|Research Institute against Cancer of the Digestive System (IRCAD), 67000 Strasbourg, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Marescaux
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.|IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.|Pôle Hépatodigestif, Unité Hépatologie, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.affiliation: IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.|Research Institute against Cancer of the Digestive System (IRCAD), 67000 Strasbourg, France.
authors.forename: Michele
authors.initials: M
authors.lastname: Diana
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.|IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.|Pôle Hépatodigestif, Unité Hépatologie, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.|Research Institute against Cancer of the Digestive System (IRCAD), 67000 Strasbourg, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pessaux
authors.affiliation: INSERM, U 1110, 67000 Strasbourg, France.|University of Strasbourg, 67000 Strasbourg, France.|IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Robinet
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods; D009368:Neoplasm Transplantation / Q000473:pathology; D014463:Ultrasonography / Q000379:methods
chemical_list: D008156:Luciferases