Molecular magnetic resonance imaging of liver inflammation using an oxidatively activated probe.
Drug-induced liver injury
Reactive oxygen species
Steatohepatitis
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
19
08
2022
revised:
06
07
2023
accepted:
10
07
2023
medline:
11
10
2023
pubmed:
11
10
2023
entrez:
11
10
2023
Statut:
epublish
Résumé
Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify liver inflammation has been underdeveloped. The inflammatory liver microenvironment is aberrantly oxidising owing in part to reactive oxygen species generated by myeloid leucocytes. We hypothesised that magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of liver inflammation. A mouse model of drug-induced liver injury was generated through intraperitoneal injection of a hepatoxic dose of acetaminophen. A mouse model of steatohepatitis was generated via a choline-deficient, l-amino acid defined high-fat diet (CDAHFD). Images were acquired dynamically before and after intravenous injection of Fe-PyC3A. The contrast agent gadoterate meglumine was used as a non-oxidatively activated negative control probe in mice fed CDAHFD. The (post-pre) Fe-PyC3A injection change in liver For mice receiving i.p. injections of acetaminophen, intrahepatic neutrophil composition correlated poorly with liver test values but positively and significantly with ΔCNR (r = 0.64, Magnetic resonance imaging using Fe-PyC3A merits further evaluation as a non-invasive biomarker for liver inflammation. Non-invasive tests to diagnose and measure liver inflammation are underdeveloped. Inflammatory cells such as neutrophils release reactive oxygen species which creates an inflammatory liver microenvironment that can drive chemical oxidation. We recently invented a new class of magnetic resonance imaging probe that is made visible to the scanner only after chemical oxidation. Here, we demonstrate how this imaging technology could be applied as a non-invasive biomarker for liver inflammation.
Sections du résumé
Background & Aims
UNASSIGNED
Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify liver inflammation has been underdeveloped. The inflammatory liver microenvironment is aberrantly oxidising owing in part to reactive oxygen species generated by myeloid leucocytes. We hypothesised that magnetic resonance imaging using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of liver inflammation.
Methods
UNASSIGNED
A mouse model of drug-induced liver injury was generated through intraperitoneal injection of a hepatoxic dose of acetaminophen. A mouse model of steatohepatitis was generated via a choline-deficient, l-amino acid defined high-fat diet (CDAHFD). Images were acquired dynamically before and after intravenous injection of Fe-PyC3A. The contrast agent gadoterate meglumine was used as a non-oxidatively activated negative control probe in mice fed CDAHFD. The (post-pre) Fe-PyC3A injection change in liver
Results
UNASSIGNED
For mice receiving i.p. injections of acetaminophen, intrahepatic neutrophil composition correlated poorly with liver test values but positively and significantly with ΔCNR (r = 0.64,
Conclusions
UNASSIGNED
Magnetic resonance imaging using Fe-PyC3A merits further evaluation as a non-invasive biomarker for liver inflammation.
Impact and implications
UNASSIGNED
Non-invasive tests to diagnose and measure liver inflammation are underdeveloped. Inflammatory cells such as neutrophils release reactive oxygen species which creates an inflammatory liver microenvironment that can drive chemical oxidation. We recently invented a new class of magnetic resonance imaging probe that is made visible to the scanner only after chemical oxidation. Here, we demonstrate how this imaging technology could be applied as a non-invasive biomarker for liver inflammation.
Identifiants
pubmed: 37818152
doi: 10.1016/j.jhepr.2023.100850
pii: S2589-5559(23)00181-7
pmc: PMC10561122
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100850Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
EMG holds equity in, and receives consulting income from Reveal Pharmaceuticals, and receives consulting income from Collagen Medical, LLC. PC holds equity in, and receives consulting income from Collagen Medical LLC, holds equity in Reveal Pharmaceuticals, and has research funding from Takeda, Pliant Therapeutics, and Janssen. Please refer to the accompanying ICMJE disclosure forms for further details.
Références
Magn Reson Med. 2004 Jan;51(1):35-45
pubmed: 14705043
J Am Chem Soc. 2015 Dec 16;137(49):15548-57
pubmed: 26588204
J Hepatol. 2019 Jun;70(6):1222-1261
pubmed: 30926241
J Clin Transl Res. 2017 Feb;3(Suppl 1):157-169
pubmed: 28670625
US Gastroenterol Hepatol Rev. 2010 Jan 1;6:73-80
pubmed: 21874146
Radiology. 2020 Jan;294(1):98-107
pubmed: 31743083
Adv Hepatol. 2014 Nov 30;2014:
pubmed: 26436133
J Hepatol. 2009 Aug;51(2):371-9
pubmed: 19501928
Hepatology. 2011 Jul;54(1):344-53
pubmed: 21520200
Hepatology. 2017 Mar;65(3):907-919
pubmed: 27880989
Hepatol Int. 2016 Jan;10(1):1-98
pubmed: 26563120
Hepatology. 2005 Jun;41(6):1313-21
pubmed: 15915461
Radiology. 2018 Mar;286(3):865-872
pubmed: 29117483
J Hepatol. 2019 Jan;70(1):151-171
pubmed: 30266282
Eur Radiol. 2003 Jun;13(6):1266-76
pubmed: 12764641
Hepatology. 1996 Aug;24(2):289-93
pubmed: 8690394
Hepatology. 2018 Jul;68(1):349-360
pubmed: 29222917
J Hepatol. 2021 Oct;75(4):810-819
pubmed: 34126105
Hepatol Commun. 2019 Nov 05;4(2):185-192
pubmed: 32025604
J Hepatol. 1995 Jun;22(6):696-9
pubmed: 7560864
J Am Chem Soc. 2019 Apr 10;141(14):5916-5925
pubmed: 30874437
Magn Reson Med. 2008 Nov;60(5):1122-34
pubmed: 18956464
Invest Radiol. 2021 Apr 1;56(4):261-270
pubmed: 33136686
Radiology. 2015 Jul;276(1):228-32
pubmed: 25942417
Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 2):S4-8
pubmed: 12471082
Curr Hepatol Rep. 2016 Jun;15(2):86-95
pubmed: 27795938
Abdom Radiol (NY). 2016 Sep;41(9):1744-50
pubmed: 27108126
Gut. 2010 Feb;59(2):258-66
pubmed: 19919948
Invest Radiol. 2019 Nov;54(11):697-703
pubmed: 31356382
World J Hepatol. 2018 Jan 27;10(1):1-7
pubmed: 29399273
Am J Gastroenterol. 2007 Apr;102(4):780-8
pubmed: 17222323
Int J Exp Pathol. 2013 Apr;94(2):93-103
pubmed: 23305254
Clin Liver Dis. 2020 Feb;24(1):89-106
pubmed: 31753253
Hepatology. 2020 Feb;71(2):510-521
pubmed: 30582669
Mod Pathol. 2017 May;30(5):773-783
pubmed: 28106105
Hepatology. 2008 Jul;48(1):169-76
pubmed: 18537184
PLoS Biol. 2020 Jul 14;18(7):e3000411
pubmed: 32663221
AJR Am J Roentgenol. 2014 Sep;203(3):643-8
pubmed: 25148170
Mol Pharm. 2008 Jul-Aug;5(4):496-504
pubmed: 18611037
J Am Soc Nephrol. 2006 Sep;17(9):2359-62
pubmed: 16885403
Radiology. 2022 Feb;302(2):270-273
pubmed: 34783590
Radiology. 2017 Aug;284(2):390-400
pubmed: 28358240
J Hepatol. 2017 Aug;67(2):370-398
pubmed: 28427875
Hepatology. 1981 Sep-Oct;1(5):431-5
pubmed: 7308988
AJR Am J Roentgenol. 2015 Mar;204(3):W302-13
pubmed: 25714316
Gastroenterology. 2016 Mar;150(3):626-637.e7
pubmed: 26677985
Radiology. 2016 Mar;278(3):782-91
pubmed: 26348104
Invest Radiol. 2020 Apr;55(4):209-216
pubmed: 31895219
Histopathology. 2012 Jan;60(2):236-48
pubmed: 21668470
J Clin Invest. 2017 Jan 3;127(1):55-64
pubmed: 28045404