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ImmunoPET of trophoblast cell-surface antigen 2 (Trop-2) expression in pancreatic cancer

  • Original Article
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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Without a standard test for pancreatic carcinomas, this highly lethal disease is normally diagnosed at its advanced stage, leading to a low survival rate of patients. Trophoblast cell-surface antigen 2 (Trop-2), a transmembrane glycoprotein, is associated with cell proliferation and highly expressed in most of solid epithelial tumors, including pancreatic cancer. A non-invasive method of imaging Trop-2 would greatly benefit clinical diagnosis and monitoring of pancreatic cancer. In the current study, 89Zr-labeled anti-Trop-2 antibody (AF650) was recruited for the systemic evaluation of Trop-2 as an immunoPET target for pancreatic cancer imaging.

Methods

AF650 was conjugated with desferrioxamine (DFO) and then radiolabeled with 89Zr. Trop-2 expression levels were determined in three pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and AsPC-1) via western blot, flow cytometry, saturation binding assay, and immunofluorescence staining. The targeting capacity of 89Zr-DFO-AF650 was evaluated in mouse models with subcutaneous xenograft of pancreatic cancers via PET imaging and bio-distribution studies. In addition, a Trop-2-positive orthotopic cancer model was recruited for further validating the targeting specificity of 89Zr-DFO-AF650.

Results

BxPC-3 cells expressed high levels of Trop-2, while AsPC-1 and MIA PaCa-2 cells expressed low levels of Trop-2. Additionally, 89Zr-DFO-AF650 exhibited high specificity to Trop-2 in BxPC-3 cells (Kd = 22.34 ± 2.509 nM). In subcutaneous xenograft models, about 28.8 ± 7.63%ID/g tracer accumulated in the BxPC-3 tumors at 120 h post injection, which was much higher than those reaching MIA PaCa-2 (6.76 ± 2.08%ID/g) and AsPC-1 (3.51 ± 0.69%ID/g) tumors (n = 4). More importantly, 89Zr-DFO-AF650 could efficiently distinguish primary tumors in the orthotopic BxPC-3 cancer model, showing high correlation between PET imaging and bio-distribution and sensitivity.

Conclusions

89Zr-DFO-AF650 can be effectively used to detect pancreatic cancer via Trop-2-mediated immunoPET in vivo, clearly revealing the great potential of Trop-2-based non-invasive imaging in pancreatic cancer detection and treatment monitoring.

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Funding

This study is financially supported by the University of Wisconsin-Madison and the National Institutes of Health (P30CA014520).

Author information

Author notes

  1. Weiyu Chen and Miao Li contributed equally to this work.

Authors and Affiliations

  1. The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, China

    Weiyu Chen & Min Zhou

  2. Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, 53792, USA

    Weiyu Chen, Miao Li, Muhsin H. Younis, Todd E. Barnhart, Dawei Jiang, Tuanwei Sun, Jonathan W. Engle & Weibo Cai

  3. International Institutes of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China

    Weiyu Chen

  4. Department of Cancer Precision Medicine, Med-X Institute, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Miao Li

  5. University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA

    Joshua M. Lang & Weibo Cai

  6. Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Joshua M. Lang

  7. Institute of Translational Medicine, Zhejiang University, Hangzhou, 310009, China

    Min Zhou

Authors
  1. Weiyu Chen
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Corresponding authors

Correspondence to Min Zhou or Weibo Cai.

Ethics declarations

Research involving human participants and/or animals

The current study does not include any studies associated with human participants. And this work follows all applicable guidelines (international, national, and/or institutional) for the care and use of animals.

Conflict of interest

Weibo Cai is a scientific advisor, stockholder, and grantee of Focus-X Therapeutics, Inc. All other authors declare that they have no conflict of interest.

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This article is part of the Topical Collection on Preclinical Imaging

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Chen, W., Li, M., Younis, M.H. et al. ImmunoPET of trophoblast cell-surface antigen 2 (Trop-2) expression in pancreatic cancer. Eur J Nucl Med Mol Imaging 49, 861–870 (2022). https://doi.org/10.1007/s00259-021-05563-1

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  • DOI: https://doi.org/10.1007/s00259-021-05563-1

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