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

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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.

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Acknowledgements

We thank Ms. Kathryn Elizabeth Day and Mr. William Packwood for their assistance in the PET imaging studies.

Funding

This work was supported by the National Institute of Biomedical Imaging and Bioengineering grant (R21-EB020737) and the American Cancer Society Research Scholar (no. ACS-RSG-17–004-01-CCE). Preclinical PET/CT imaging was supported in part by P30CA047904 (UPCI CCSG).

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Authors and Affiliations

  1. Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, 97229, USA

    Lingyi Sun, Zhonghan Li & Dexing Zeng

  2. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Lingyi Sun, Yongkang Gai, Huiqiang Li, Jianchun Li & Dexing Zeng

  3. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, 97229, USA

    John Muschler

  4. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Rui Kang & Daolin Tang

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  1. Lingyi Sun
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Sun, L., Gai, Y., Li, Z. et al. Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer. Mol Imaging Biol 24, 580–589 (2022). https://doi.org/10.1007/s11307-022-01704-6

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