Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics.
bioRxiv
; 2024 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-38249519
ABSTRACT
We apply spatial transcriptomics and proteomics to select pancreatic cancer surface receptor targets for molecular imaging and theranostics using an approach that can be applied to many cancers. Selected cancer surfaceome epithelial markers were spatially correlated and provided specific cancer localization, whereas the spatial correlation between cancer markers and immune- cell or fibroblast markers was low. While molecular imaging of cancer-associated fibroblasts and integrins has been proposed for pancreatic cancer, our data point to the tight junction protein claudin-4 as a theranostic target. Claudin-4 expression increased â¼16 fold in cancer as compared with normal pancreas, and the tight junction localization conferred low background for imaging in normal tissue. We developed a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to â¼25% injected activity per cc (IA/cc) in metastases and â¼18% IA/cc in tumors. Our work motivates a new approach for data-driven selection of molecular targets.
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MEDLINE
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En
Ano de publicação:
2024
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Article