Abstract
PurposeDespite 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.ProceduresThe 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.ResultsHigh 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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types as it has an extremely poor 5-year survival rate of G 5 % [1]
The positron emission tomography (PET) radiotracer 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) is the standard clinical option for suspected PDAC; it has been shown to be largely ineffective for the detection of small (≤ 20 mm) pancreatic tumours, and in most cases inferior to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of liver, peritoneal and lung metastases. [18F]FDG is unable to distinguish focal mass-forming pancreatitis from pancreatic cancer in most cases [5]
As clinical applications of fluorescence imaging are limited due to considerable signal attenuation by tissue, we subsequently developed a C-terminal fragment of CPE (cCPE) derivative modified with the single-photon emission computed tomography (SPECT) radioisotope indium-111 ([111In]cCPE-GST) [13]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types as it has an extremely poor 5-year survival rate of G 5 % [1] This dismal prognosis is due in part to the asymptomatic progression of this malignancy in Torres J.B. et al.: Imaging of Claudin-4 in Pancreatic Ductal Adenocarcinoma its early stages and the lack of adequate screening measures, resulting in 80–90 % of patients being diagnosed when the disease is already in an advanced, metastatic state. [18F]FDG is unable to distinguish focal mass-forming pancreatitis from pancreatic cancer in most cases [5] These limitations strongly indicate the need for alternative biomarkers which arise during the early stages of PDAC formation that can be measured noninvasively by molecular imaging techniques
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
