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

Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]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, [In-111]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. The ability of [In-111]anti-claudin-4 mAb to selectively target claudin-4 was assessed using two human xenograft tumour models with differential claudin-4 status in mice. [In-111]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 [F-18]FDG-PET, magnetic resonance imaging (MRI), histology, and immunofluorescence microscopy. High uptake of [In-111]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 [In-111]anti-claudin-4 mAb also enabled clear visualisation of spontaneous PDAC formation in KPC mice. [In-111]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.