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ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers

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

Abstract

Purpose

The high expression of the transmembrane glycoprotein trophoblast cell-surface antigen 2 (Trop2) was strongly associated with the progression of solid tumors, including pancreatic and gastric cancers. Our study aimed to construct Trop2-specific immuno-positron emission tomography (immunoPET) probes and assess the diagnostic abilities in preclinical pancreatic and gastric cancer models.

Methods

The expression of Trop2 in pancreatic cancer was determined by single-cell sequencing and immunohistochemistry on tissue microarray (TMA). Flow cytometry was used to screen the expression of Trop2 in pancreatic cancer cell lines. Two nanobodies (i.e., RTD98 and RTD01) targeting Trop2 were developed and labeled with gallium-68 (68Ga, T1/2 = 1.1 h) to construct immunoPET imaging probes. The agents were researched in cell-derived pancreatic and patient-derived gastric cancer models expressing varying Trop2.

Results

Single-cell sequencing results showed high expression of Trop2 in pancreatic ductal cells as well as acinar cells and immunohistochemical staining of TMA from pancreatic cancers showed significantly higher expression of Trop2 in cancerous than in paracancerous tissues. ImmunoPET utilizing [68Ga]Ga-NOTA-RTD98 could clearly delineate subcutaneous tumors, both in cell-derived pancreatic cancer models and patient-derived gastric cancer models, superior to imaging using [18F]-FDG or a non-specific probe [68Ga]Ga-NOTA-RTD161. Another probe with improved pharmacokinetics targeting Trop2, [68Ga]Ga-NOTA-RTD01, was further prepared and showed advantageous diagnostic capabilities in preclinical pancreatic cancer models.

Conclusion

In the work, we reported two nanobody tracers targeting human Trop2 which may facilitate better use of Trop2-targeted therapeutics by noninvasively displaying expression dynamics of the target.

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Data availability

The original data of the work can be obtained from Prof. Weijun Wei upon rational request.

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Acknowledgements

The work was supported in part by the National Key Research and Development Program of China (Grant No. 2021YFA0910000), and the National Natural Science Foundation of China (Grant No. 82372014, 82171972, and 82001878).

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Author notes

  1. Wei Huang and Chenyi Liang contributed equally to the work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Wei Huang, Chenyi Liang, You Zhang, Di Zhang, Shuxian An, Qianyun Wu, Jiajin Li, Haitao Zhao, Cheng Wang, Gang Huang, Weijun Wei & Jianjun Liu

  2. Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Jiujie Cui

  3. Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Zhouzhou Bao

  4. Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Zhouzhou Bao

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  1. Wei Huang
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Contributions

W. Wei, J. Liu, and G. Huang collaboratively conceived and designed the project. W. Huang and C. Liang performed the experiments with the help of S. An, Y. Zhang, D. Zhang. W. Huang and C. Liang wrote most of the manuscript, while others contributed to the writing. J. Cui provided support in TMA analysis. G. Huang and Z. Bao provided inputs in the initial design of the project and revised the manuscript. W. Wei and J. Liu supervised the study and revised and finalized the manuscript.

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Correspondence to Weijun Wei or Jianjun Liu.

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Conflict of interest

W. Wei, W. Huang, and J. Liu are co-inventors on a provisional patent application encompassing the technology reported in the manuscript. W. Wei is a consultant of Alpha Nuclide (Ningbo) Medical Technology Co., Ltd.

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Huang, W., Liang, C., Zhang, Y. et al. ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers. Eur J Nucl Med Mol Imaging 51, 380–394 (2024). https://doi.org/10.1007/s00259-023-06454-3

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