Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody
<strong>Purpose:</strong> Despite its widespread use, the 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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
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Springer US
2017
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| _version_ | 1797104413705240576 |
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| author | Torres, J Knight, JC Mosley, MJ Kersemans, V Koustoulidou, S Allen, D Kinchesh, P Smart, S Cornelissen, B |
| author_facet | Torres, J Knight, JC Mosley, MJ Kersemans, V Koustoulidou, S Allen, D Kinchesh, P Smart, S Cornelissen, B |
| author_sort | Torres, J |
| collection | OXFORD |
| description | <strong>Purpose:</strong> Despite its widespread use, the 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. <strong>Procedures:</strong> 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- positron emission tomography (PET), magnetic resonance imaging (MRI), histology, and immunofluorescence microscopy. <strong>Results:</strong> High uptake of [111In]anti-claudin-4 mAb was observed in pancreatic duct epithelioid carcinoma 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. <strong>Conclusions:</strong> [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. |
| first_indexed | 2024-03-07T06:33:26Z |
| format | Journal article |
| id | oxford-uuid:f6cd12ea-4186-44d5-aced-1074631896bc |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:33:26Z |
| publishDate | 2017 |
| publisher | Springer US |
| record_format | dspace |
| spelling | oxford-uuid:f6cd12ea-4186-44d5-aced-1074631896bc2022-03-27T12:37:46ZImaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibodyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f6cd12ea-4186-44d5-aced-1074631896bcSymplectic Elements at OxfordSpringer US2017Torres, JKnight, JCMosley, MJKersemans, VKoustoulidou, SAllen, DKinchesh, PSmart, SCornelissen, B<strong>Purpose:</strong> Despite its widespread use, the 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. <strong>Procedures:</strong> 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- positron emission tomography (PET), magnetic resonance imaging (MRI), histology, and immunofluorescence microscopy. <strong>Results:</strong> High uptake of [111In]anti-claudin-4 mAb was observed in pancreatic duct epithelioid carcinoma 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. <strong>Conclusions:</strong> [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. |
| spellingShingle | Torres, J Knight, JC Mosley, MJ Kersemans, V Koustoulidou, S Allen, D Kinchesh, P Smart, S Cornelissen, B Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title | Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title_full | Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title_fullStr | Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title_full_unstemmed | Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title_short | Imaging of claudin-4 in pancreatic ductal adenocarcinoma using a radiolabelled anti-claudin-4 monoclonal antibody |
| title_sort | imaging of claudin 4 in pancreatic ductal adenocarcinoma using a radiolabelled anti claudin 4 monoclonal antibody |
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