Dynamic Molecular Imaging for Hepatic Function Assessment in Mice: Evaluation in Endotoxin-Induced and Warm Ischemia-Reperfusion Models of Acute Liver Failure Felicie Sherer 1* , Gaetan Van Simaeys 1 , Jesper Kers 2,3 , Qing Yuan 2,4 , Gilles Doumont 1 , Marie-Aline Laute 1 , Cindy Peleman 5 , Dominique Egrise 1 , Tony Lahoutte 5 , Veronique Flamand 2 and Serge Goldman 1 1 Center for Microscopy and Molecular Imaging (CMMI) and Department of Nuclear Medicine, Erasme Hospital, Free University of Brussels (ULB), Belgium 2 Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Gosselies, Belgium 3 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands 4 Organ Transplant Center, The 309th Hospital of PLA, Beijing, China 5 In vivo Cellular and Molecular Imaging (ICMI) Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium *Corresponding author: Felicie Sherer, CMMI, 8 rue Adrienne Bolland, B-6041 Gosselies, Belgium, Tel: +32(0)2650 9789; Fax:+32(0)2 650 9795; E-mail: fsherer@ulb.ac.be Received September 29 2014, Accepted November 14 2014, Published November 19 2014 Copyright: © 2014 Sherer F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background: In hepatic transplantation, inflammatory response related to liver ischemia-reperfusion injury is an important cause of hepatocellular damage that may lead to organ dysfunction. This project aims to develop a new method of dynamic imaging for the local analysis of hepatic function using un-metabolized 99mTc-labeled mebrofenin excretion time in the bile canaliculi as a read-out. Methods: C57BL/6 female mice underwent acute liver damage induced either by endotoxin administration or by warm ischemia-reperfusion. Liver damage intensity was assessed with a 99mTc-labeled mebrofenin dynamic planar imaging protocol, together with biological parameters of liver damage — levels of blood transaminases, liver necrosis and neutrophil infiltration. The acquisition data consisted of a series of 60-frame pinhole images performed on a gamma camera A region of interest was drawn within the hepatic area in order to measure liver activity on each frame. Excretion rate was quantified as the time necessary for the count value to reach 50% (T0.5Exc) and 20% (T0.2Exc) of the maximum liver count value. We compared biological parameters of liver damage — levels of blood transaminases, liver necrosis and neutrophil infiltration — with 99mTc-labeled mebrofenin excretion times in both models of liver damage and in control animals. Results: 99mTc-labeled mebrofenin excretion times (T0.5Exc and T0.2Exc) were significantly increased in both models of liver damage. Conclusions: We concluded that quantification of liver function is feasible in mice using dynamic planar pinhole imaging with 99mTc-mebrofenin as tracer of the hepato-biliary function. This method is particularly suited to the non- invasive evaluation of immune and pharmacological interventions aiming at a reduction of early liver insults related to ischemic-reperfusion phenomenon. Keywords: Molecular imaging; Liver; Ischemia-reperfusion; Mebrofenin Abbreviations DAMPs: Damage Associated Molecular Pattern Molecules; ET: Endothelin; HIDA: Hepatic Iminodiacetic Acid; HMGB-1: the nuclear protein High Mobility Group Box 1; IRI: Ischemia-Reperfusion Injury; IR2h: group of mice Imaged 2 hours After Hepatic Reperfusion; IR24h: group of mice Imaged 24 hours After Hepatic Reperfusion; LPS: Lipopolysaccharide; MRP: Multidrug Resistance Proteins; NO: Nitric Oxide; NLRs: NOD-Like Receptor Pathways; OATP: The Main Salt and Organic Anion Transporters; PAMPs: Pathogen Associated Molecular Pattern Molecules; RNS: Reactive Nitrogen Species; ROS: Reactive Oxygen Species; sALT: Serum Alanine Aminotransferase; sAST: Serum Aspartate Aminotransferase; SPECT: Single Photon Emission Computed Tomography; TLR: Toll-Like Receptor; TLRs: Toll-Like Receptor Pathways Introduction Ischemia-reperfusion injury (IRI) refers to the cellular damage induced by oxygen delivery restoration in an organ subjected to a hypoxic insult [1]. Liver IRI occurs in many common clinical situations including extensive liver injury, major liver resection, haemorrhagic shock and liver transplantation. Postsurgical liver dysfunction or failure is strongly linked to the extent of hepatic IRI and is an expected consequence of these heavy liver surgical procedures [2]. Bacterial cell wall lipopolysaccharide (LPS) is a typical agent used in animal models of endotoxin-induced liver injury [3]. Indeed, LPS is a trigger for cytokine formation through the activation of the TLR-4 pathway; at a high dose it directly activates the Liver Sherer et al., J Liver 2014, 3:5 http://dx.doi.org/10.4172/2167-0889.1000170 Research article Open Access J Liver ISSN:2167-0889 J Liver, an open access journal Volume 3 • Issue 5 • 1000170