Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: an Imaging Study
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RESEARCH ARTICLE
Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: an Imaging Study Marie-Aline Neveu,1 Nicolas Beziere,1 Rolf Daniels,2 Caroline Bouzin,3 Arnaud Comment,4 Johannes Schwenck,1,5,6 Kerstin Fuchs,1 Manfred Kneilling,1,6,7 Bernd J. Pichler,1,6 Andreas M. Schmid 1 1
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Roentgenweg 13, 72076, Tuebingen, Germany 2 Department of Pharmaceutical Technology, Eberhard Karls University Tuebingen, Tuebingen, Germany 3 IREC Imaging Platform, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium 4 General Electric Healthcare, Pollards Wood, Nightingales Lane, Chalfont St Giles, UK 5 Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, Tuebingen, Germany 6 Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Tuebingen, Germany 7 Department of Dermatology, Eberhard Karls University Tuebingen, Tuebingen, Germany
Abstract Purpose: Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-13C-pyruvate magnetic resonance spectroscopy (MRS) and 19F magnetic resonance imaging (MRI), respectively. Procedure: Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-13C-pyruvate into hyperpolarized 1-13Clactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles.
Manuscript submitted as an original article to Molecular Imaging and Biology Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01510-y) contains supplementary material, which is available to authorized users. Correspondence to: Andreas Schmid; e-mail: [email protected]
Neveu M.-A. et al.: Immunometabolic imaging of experimental RA
Results: Hyperpolarized 1-13C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum
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