Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer

Lingyi Sun, Yongkang Gai, Zhonghan Li, Huiqiang Li, Jianchun Li, John Muschler, Rui Kang, Daolin Tang, Dexing Zeng

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal gastrointestinal cancer, and its poor prognosis is highly associated with the lack of an efficient early detection technology. Here, we report that RGD-NGR heterodimer labeled with PET isotope could be applied in PDAC early detection. Procedures: The RGD-NGR tracer was first compared with its corresponding monomeric counterparts via PET imaging studies using mice bearing a subcutaneous BxPC3 tumor. Subsequently, the RGD-NGR tracer was evaluated in autochthonous mouse models with spontaneously developed late stage PanIN lesions (KCER mice) or PDAC (KPC mice) via both PET imaging studies and ex vivo biodistribution studies. Furthermore, a comparison between 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) and the RGD-NGR tracer was conducted via PET imaging of the same KCH mouse bearing spontaneously developed PDAC. H&E staining was performed to confirm the malignant pancreatic tissue in the KCH mouse. Immunofluorescence staining was performed to confirm the expression of integrin αVβ3 and CD13. Results: The RGD-NGR tracer exhibited improved in vivo performance as compared with its corresponding monomeric counterparts on the subcutaneous BxPC3 tumor mouse model. Subsequent evaluation in autochthonous mouse models demonstrated its capability to detect both pre-malignant and malignant pancreases. Further comparison with [18F]F-FDG revealed the superiority of the proposed heterodimer in imaging spontaneously developed PDAC. H&E staining confirmed the malignant pancreatic tissue in the KCH mouse, while the expression of both integrin αVβ3 and CD13 receptors was demonstrated with immunofluorescence staining. Conclusion: The proposed RGD-NGR heterodimer possesses the potential to be applied in the PDAC early detection for high-risk populations.

Original languageEnglish (US)
Pages (from-to)580-589
Number of pages10
JournalMolecular Imaging and Biology
Volume24
Issue number4
DOIs
StatePublished - Aug 2022

Keywords

  • CD13
  • Early detection
  • Integrin αβ
  • PET
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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