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In vivo detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy

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Item Type:Article
Title:In vivo detection of teriflunomide-derived fluorine signal during neuroinflammation using fluorine MR spectroscopy
Creators Name:Prinz, C. and Starke, L. and Millward, J.M. and Fillmer, A. and Delgado, P.R. and Waiczies, H. and Pohlmann, A. and Rothe, M. and Nazaré, M. and Paul, F. and Niendorf, T. and Waiczies, S.
Abstract:BACKGROUND: Magnetic resonance imaging (MRI) is indispensable for diagnosing neurological conditions such as multiple sclerosis (MS). MRI also supports decisions regarding the choice of disease-modifying drugs (DMDs). Determining in vivo tissue concentrations of DMDs has the potential to become an essential clinical tool for therapeutic drug monitoring (TDM). The aim here was to examine the feasibility of fluorine-19 ((19)F) MR methods to detect the fluorinated DMD teriflunomide (TF) during normal and pathological conditions. METHODS: We used (19)F MR spectroscopy to detect TF in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS) in vivo. Prior to the in vivo investigations we characterized the MR properties of TF in vitro. We studied the impact of pH and protein binding as well as MR contrast agents. RESULTS: We could detect TF in vivo and could follow the (19)F MR signal over different time points of disease. We quantified TF concentrations in different tissues using HPLC/MS and showed a significant correlation between ex vivo TF levels in serum and the ex vivo (19)F MR signal. CONCLUSION: This study demonstrates the feasibility of (19)F MR methods to detect TF during neuroinflammation in vivo. It also highlights the need for further technological developments in this field. The ultimate goal is to add (19)F MR protocols to conventional (1)H MRI protocols in clinical practice to guide therapy decisions.
Keywords:MRI, MRS, Fluorine, Teriflunomide, Magnetic Resonance Spectroscopy, Experimental Autoimmune Encephalomyelitis, Multiple Sclerosis, Animals, Mice, Rats
Publisher:Ivyspring International Publisher
Page Range:2490-2504
Date:1 January 2021
Official Publication:https://doi.org/10.7150/thno.47130
PubMed:View item in PubMed

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