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

James Wang, Jai Woong Seo, Aris J. Kare, Martin Schneider, Mallesh Pandrala, Spencer K. Tumbale, Marina N. Raie, Gokce Engudar, Nisi Zhang, Yutong Guo, Xiaoxu Zhong, Sofia Ferreira, Bo Wu, Laura D. Attardi, Guillem Pratx, Andrei Iagaru, Ryan L. Brunsing, Gregory W. Charville, Walter G. Park and Katherine W. Ferrara ()
Additional contact information
James Wang: Stanford University
Jai Woong Seo: Stanford University
Aris J. Kare: Stanford University
Martin Schneider: Stanford University
Mallesh Pandrala: Stanford University
Spencer K. Tumbale: Stanford University
Marina N. Raie: Stanford University
Gokce Engudar: Stanford University
Nisi Zhang: Stanford University
Yutong Guo: Stanford University
Xiaoxu Zhong: Stanford University
Sofia Ferreira: Stanford University
Bo Wu: Stanford University
Laura D. Attardi: Stanford University
Guillem Pratx: Stanford University
Andrei Iagaru: Stanford University
Ryan L. Brunsing: Stanford University
Gregory W. Charville: Stanford University
Walter G. Park: Stanford University
Katherine W. Ferrara: Stanford University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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 ~16 fold 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.

Date: 2024
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DOI: 10.1038/s41467-024-54761-6

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