CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Published: April 2018
AI Article Synopsis
Article Abstract
Purpose: Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[F]fluoro-D-glucose ([F]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]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 [In]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]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]FDG-PET, magnetic resonance imaging (MRI), histology, and immunofluorescence microscopy.
Results: High uptake of [In]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]anti-claudin-4 mAb also enabled clear visualisation of spontaneous PDAC formation in KPC mice.
Conclusions: [In]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.
CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Purpose: Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[F]fluoro-D-glucose ([F]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]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.
Claudin-4 (CLDN4) is a tetraspanin transmembrane protein of tight junction structure and is highly expressed in pancreatic and ovarian cancers. In this study, we aimed to generate an anti-Claudin-4 monoclonal antibody (mAb) and evaluate its antitumor efficacy in vitro and in vivo. To isolate specific mAb, we generated CLDN3, 4, 5, 6, and 9, expressing Chinese hamster ovary (CHO) cells, and then used them as positive and negative targets through cell-based screening.
