Development of a novel 18F-labeled small molecule probe for PET imaging of mesenchymal epithelial transition receptor expression.
The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternativ...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 51; no. 3; pp. 656 - 669 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Feb2024
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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=174879058&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 174879058 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: Feb2024 vid: 51 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 174879058 173486665 10.1007/s00259-023-06495-8 174879058 ppf: 656 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Development of a novel 18F-labeled small molecule probe for PET imaging of mesenchymal epithelial transition receptor expression. aug: au: Bu, Lihong Ma, Xiaowei Ji, Aiyan Geng, Kaijun Feng, Hongyan Li, Li Zhang, Ao Cheng, Zhen affil: https://ror.org/03ekhbz91 PET-CT/MRI Center, Renmin Hospital of Wuhan University, 430060, Wuhan, China sug: ab: The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternative tool for visualizing whole-body c-Met expression quantitatively and noninvasively. Here we firstly reported an 18F labeled, small-molecule quinine compound-based PET probe, 1-(4-(5-amino-7-(trifluoromethyl) quinolin-3-yl) piperazin-1-yl)-2-(fluoro-[18F]) propan-1-one, herein referred as [18F]-AZC. Methods: [18F]-AZC was synthesized via a one-step substitution reaction and characterized by radiochemistry methods. [18F]-AZC specificity and affinity toward c-Met were assessed by cell uptake assay, with or without cold compound [19F]-AZC or commercial c-Met inhibitor blocking. MicroPET/CT imaging and biodistribution studies were conducted in subcutaneous murine xenografts of glioma. Additionally, [18F]-AZC was then further evaluated in orthotopic glioma xenografts, by microPET/CT imaging accompanied with MRI and autoradiography for co-registration of the tumor. Immunofluorescence staining was also carried out to qualitatively evaluate the c-Met expression in tumor tissue, co-localizes with H&E staining. Results: This probe shows easy radiosynthesis, high stability in vitro and in vivo, high targeting affinity, and favorable lipophilicity and brain transport coefficient. [18F]-AZC demonstrates excellent tumor imaging properties in vivo and can delineate c-Met positive glioma specifically at 1 h after intravenous injection of the probe. Moreover, favorable correlation was observed between the [18F]-AZC accumulation and the amount of c-Met expression in tumor. Conclusion: This novel imaging probe could be applied as a valuable tool for management of anti-c-Met therapies in patients in the future. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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