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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.

Original publication

DOI

10.1007/s11307-017-1112-8

Type

Journal article

Journal

Mol Imaging Biol

Publication Date

04/2018

Volume

20

Pages

292 - 299

Keywords

Claudin-4, Molecular imaging, Pancreatic ductal adenocarcinoma, SPECT, Adenocarcinoma, Animals, Antibodies, Monoclonal, Autoradiography, Carcinoma, Pancreatic Ductal, Claudin-4, Humans, Imaging, Three-Dimensional, Indium Radioisotopes, Mice, Inbred BALB C, Mice, Nude, Pentetic Acid, Radiopharmaceuticals, Reproducibility of Results, Tissue Distribution, Xenograft Model Antitumor Assays