Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics

Sep 21, 2026

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Spatial transcriptomic analysis and proteomics of human surgical samples identify pancreatic ductal adenocarcinoma (PDAC) targets for positron emission tomography (PET) theranostics. Cancer cell surface markers show strong spatial correlation and enable precise cancer localization, while correlations with immune-related or fibroblast markers remain low. Claudin-4 increases ~16-fold in cancer and tight junction localization reduces normal-tissue background. A claudin-4–targeted peptide imaging agent accumulates to ~25% IA/cc in metastases and ~18% IA/cc in tumors, supporting a data-driven target selection strategy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Background and clinical need

Imaging limitations in PDAC

Target selection rationale

Cancer-marker spatial correlation

Claudin-4 and tight junction exposure

Imaging agent development and performance

Tumor and metastasis accumulation

Article [https://doi.org/10.1038/s41467-024-54761-6](https://doi.org/10.1038/s41467-024-54761-6) Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics Received: 4 January 2024 | Accepted: 19 November 2024 | | --- | | | | Check for updates | James Wang1,9, Jai Woong Seo 1,9, Aris J. Kare 1,2,9, Martin Schneider 1, Mallesh Pandrala1, Spencer K. Tumbale 1, Marina N. Raie 1, Gokce Engudar1, Nisi Zhang 1, Yutong Guo1, Xiaoxu Zhong 3, Soﬁa Ferreira3, Bo Wu1, Laura D. Attardi 3,4, Guillem Pratx 3, Andrei Iagaru5, Ryan L. Brunsing6, Gregory W. Charville 7, Walter G. Park8 & Katherine W. Ferrara 1 Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated ﬁbroblasts and integrins have been proposed as targets for imaging of pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics and proteomics of human surgical samples are applied to select PDAC targets. We ﬁnd that selected cancer cell surface markers are spatially correlated and provide speciﬁc cancer localization, whereas the spatial correlation between cancer markers and immune-related or ﬁbroblast markers is low. Claudin-4 expression increases~16fold in cancer as compared with normal pancreas, and tight junction localization confers low background for imaging in normal tissue. We develop a peptide-based molecular imaging agent targeted to claudin- 4 with accumulation to ~25% injected activity per cubic centimeter (IA/cc) in metastases and ~18% IA/cc in tumors. Our work motivates a data-driven approach to selection of molecular targets. Molecular Imaging (MI) is a growing biomedical discipline that enables the non-invasive visualization, characterization, and quantiﬁcation of chemical and biological processes at the cellular and subcellular levels across time in living systems. Molecular imaging can detect small cancerous lesions and provides an opportunity to assess therapeutic accumulation across a wide range of molecular therapies. Positron emission tomography (PET) uniquely quantiﬁes molecular targets by employing sub-pharmacological amounts of molecularly-speciﬁcradiolabeled agents (radiopharmaceuticals). The short radioactive half-lives used in PET imaging facilitate repeated imaging, and the latest hardware innovations enable dynamic, functional imaging of these biomarkers in situ. Improved imaging methods are needed to map pancreatic ductaladenocarcinoma (PDAC) lesions and guide therapy. Characterizing pancreatic nodules with imaging is signiﬁcant as 30-50% of the adult population may harbor precancerous lesions1–4. Invasive cancer can be present within intraductal papillary mucinous neoplasms (IPMNs), and similar mutational proﬁles to PDAC are found in incidentallydiscovered pancreatic intraepithelial neoplasms (PanINs)2. Further, PDAC is the third leading cause of cancer-related deaths as of 20245. 1Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. 2Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, USA. 3Department of Radiation Oncology, Stanford University, 857 Blake Wilbur Drive, Stanford, CA, USA. 4Department of Genetics, Stanford University, 291 Campus Drive, Stanford, CA, USA. 5Nuclear Medicine and Molecular Imaging Division, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. 6Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. 7Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. 8Department of Medicine-Gastroenterology & Hepatology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. 9These authors contributed equally: James Wang, Jai Woong Seo, Aris J. Kare. e-mail: [kwferrar@stanford.edu](kwferrar@stanford.edu) PET-CT imaging has been applied using 18F-FDG imaging of m

FAQs

Which biomarker is used to drive PET imaging in this study?

The study focuses on Claudin-4 (CLDN4), a tight-junction associated cell-surface protein with markedly increased expression in PDAC compared with normal pancreas.

How does spatial correlation affect target selection for PET imaging?

Selected cancer cell surface markers are spatially correlated with cancer localization, whereas immune-related or fibroblast markers show low spatial correlation, supporting marker-driven imaging specificity.

What imaging performance does the claudin-4–targeted peptide agent achieve?

The peptide-based imaging agent accumulates to about 25% injected activity per cubic centimeter (IA/cc) in metastases and about 18% IA/cc in tumors.

Sep 21, 2026

Uploaded by Aurelia