Toggle Main Menu Toggle Search

Open Access padlockePrints

Imaging of Claudin-4 in Pancreatic Ductal Adenocarcinoma Using a Radiolabelled Anti-Claudin-4 Monoclonal Antibody

Lookup NU author(s): Dr James Knight

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017, The Author(s). Purpose: Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been shown in clinical settings to be ineffective for improving early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A promising biomarker for PDAC detection is the tight junction protein claudin-4. The purpose of this study was to evaluate a new single-photon emission computed tomography (SPECT) imaging agent, [111In]anti-claudin-4 mAb, with regard to its ability to allow visualisation of claudin-4 in a xenograft and a genetically engineered mouse model of PDAC. Procedures: The ability of [111In]anti-claudin-4 mAb to selectively target claudin-4 was assessed using two human xenograft tumour models with differential claudin-4 status in mice. [111In]anti-claudin-4 mAb was also used to detect PDAC development in genetically engineered KPC mice. The PDAC status of these mice was confirmed with [18F]FDG-PET, magnetic resonance imaging (MRI), histology, and immunofluorescence microscopy. Results: High uptake of [111In]anti-claudin-4 mAb was observed in PDAC xenografts in mice, reaching 16.9 ± 4.5 % of injected dose per gram (% ID/g) at 72 h post-injection. This uptake was mediated specifically by the expression of claudin-4. Uptake of [111In]anti-claudin-4 mAb also enabled clear visualisation of spontaneous PDAC formation in KPC mice. Conclusions: [111In]anti-claudin-4 mAb allows non-invasive detection of claudin-4 upregulation during development of PDAC and could potentially be used to aid in the early detection and characterisation of this malignancy.


Publication metadata

Author(s): Torres JB, Knight JC, Mosley MJ, Kersemans V, Koustoulidou S, Allen D, Kinchesh P, Smart S, Cornelissen B

Publication type: Article

Publication status: Published

Journal: Molecular Imaging and Biology

Year: 2018

Volume: 20

Issue: 2

Pages: 292-299

Online publication date: 25/08/2017

Acceptance date: 02/04/2016

Date deposited: 30/08/2018

ISSN (print): 1536-1632

ISSN (electronic): 1860-2002

Publisher: Springer New York LLC

URL: https://doi.org/10.1007/s11307-017-1112-8

DOI: 10.1007/s11307-017-1112-8


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share