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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

04.10.2023 | Original Article

ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers

verfasst von: Wei Huang, Chenyi Liang, You Zhang, Di Zhang, Shuxian An, Qianyun Wu, Jiajin Li, Haitao Zhao, Cheng Wang, Jiujie Cui, Zhouzhou Bao, Gang Huang, Weijun Wei, Jianjun Liu

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2024

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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, T_1/2 = 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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Titel: ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers
verfasst von: Wei Huang
Chenyi Liang
You Zhang
Di Zhang
Shuxian An
Qianyun Wu
Jiajin Li
Haitao Zhao
Cheng Wang
Jiujie Cui
Zhouzhou Bao
Gang Huang
Weijun Wei
Jianjun Liu
Publikationsdatum: 04.10.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06454-3

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ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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