CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett's esophagus.

Animal models Barrett’s esophagus CXCR4 Dysplasia Endoscopy Esophageal cancer Fluorescence imaging Molecular imaging Peptide

Journal

EJNMMI research
ISSN: 2191-219X
Titre abrégé: EJNMMI Res
Pays: Germany
ID NLM: 101560946

Informations de publication

Date de publication:
10 Jan 2022
Historique:
received: 12 10 2021
accepted: 24 12 2021
entrez: 10 1 2022
pubmed: 11 1 2022
medline: 11 1 2022
Statut: epublish

Résumé

Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett's esophagus. Six L2-IL1B mice with advanced stage of disease (12-16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12-14 months old)  by a novel imaging system with two L2-IL1B mice used as negative controls. Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells  by confocal microscopy further confirmed the imaging results. This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett's esophagus. Further investigations are needed to assess its use in the clinical setting.

Sections du résumé

BACKGROUND BACKGROUND
Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett's esophagus.
METHODS METHODS
Six L2-IL1B mice with advanced stage of disease (12-16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12-14 months old)  by a novel imaging system with two L2-IL1B mice used as negative controls.
RESULTS RESULTS
Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells  by confocal microscopy further confirmed the imaging results.
CONCLUSIONS CONCLUSIONS
This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett's esophagus. Further investigations are needed to assess its use in the clinical setting.

Identifiants

pubmed: 35006394
doi: 10.1186/s13550-021-00875-7
pii: 10.1186/s13550-021-00875-7
pmc: PMC8748556
doi:

Types de publication

Journal Article

Langues

eng

Pagination

2

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 84: B05

Informations de copyright

© 2021. The Author(s).

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Auteurs

Sabrina Marcazzan (S)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.
Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany.
Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany.
Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Peter-Mayr-Straße 4b, 6020, Innsbruck, Austria.

Marcos J Braz Carvalho (MJ)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.

Matthias Konrad (M)

Institut für Pharmazeutische Radiochemie, Technische Universität München, Munich, Germany.

Julia Strangmann (J)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.
Innere Medizin II, Universitätsklinik Freiburg, Universität Freiburg, Freiburg im Breisgau, Germany.

Anna Tenditnaya (A)

Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany.
Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany.

Theresa Baumeister (T)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.

Roland M Schmid (RM)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.

Hans-Jürgen Wester (HJ)

Institut für Pharmazeutische Radiochemie, Technische Universität München, Munich, Germany.

Vasilis Ntziachristos (V)

Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany.
Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany.

Dimitris Gorpas (D)

Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany.
Helmholtz Zentrum München, Institute of Biological and Medical Imaging, Neuherberg, Germany.

Timothy C Wang (TC)

Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA.

Margret Schottelius (M)

Institut für Pharmazeutische Radiochemie, Technische Universität München, Munich, Germany.
Translational Radiopharmaceutical Sciences, Departments of Nuclear Medicine and Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Michael Quante (M)

II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany. michael.quante@uniklinik-freiburg.de.
Innere Medizin II, Universitätsklinik Freiburg, Universität Freiburg, Freiburg im Breisgau, Germany. michael.quante@uniklinik-freiburg.de.

Classifications MeSH