ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers.
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...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 51; no. 2; pp. 380 - 395 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jan2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=174658109&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 174658109 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Jan2024 vid: 51 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 174658109 172770735 10.1007/s00259-023-06454-3 174658109 ppf: 380 ppct: 15 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: ImmunoPET imaging of Trop2 expression in solid tumors with nanobody tracers. aug: au: Huang, Wei Liang, Chenyi Zhang, You Zhang, Di An, Shuxian Wu, Qianyun Li, Jiajin Zhao, Haitao Wang, Cheng Cui, Jiujie Bao, Zhouzhou Huang, Gang Wei, Weijun Liu, Jianjun affil: Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, 200127, Shanghai, China sug: ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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