64 Cu-Labeled Ubiquitin for PET Imaging of CXCR4 Expression in Mouse Breast Tumor.

Autor: Li H; PET-CT Center, Department of Nuclear Medicine, Henan Provincial People's Hospital, Weiwu Road, No. 7, Jinshui District, Zhengzhou, Henan CN 450003, China.; Molecular Imaging Laboratory, Department of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15219, United States., Zhang X; Molecular Imaging Laboratory, Department of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15219, United States., Wu HY; Department of Chemistry, State University of New York at Buffalo, 679 Natural Sciences Complex, Buffalo, New York 14260, United States., Sun L; Molecular Imaging Laboratory, Department of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15219, United States.; Department of Diagnostic Radiology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., CRR210B, Portland, Oregon 97239, United States., Ma Y; Molecular Imaging Laboratory, Department of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15219, United States.; Department of Diagnostic Radiology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., CRR210B, Portland, Oregon 97239, United States., Xu J; PET-CT Center, Department of Nuclear Medicine, Henan Provincial People's Hospital, Weiwu Road, No. 7, Jinshui District, Zhengzhou, Henan CN 450003, China., Lin Q; Department of Chemistry, State University of New York at Buffalo, 679 Natural Sciences Complex, Buffalo, New York 14260, United States., Zeng D; Molecular Imaging Laboratory, Department of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15219, United States.; Department of Diagnostic Radiology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., CRR210B, Portland, Oregon 97239, United States.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2019 Jul 22; Vol. 4 (7), pp. 12432-12437. Date of Electronic Publication: 2019 Jul 22 (Print Publication: 2019).
DOI: 10.1021/acsomega.9b00678
Abstrakt: Ubiquitin has been recently identified as a chemokine receptor 4 (CXCR4) natural ligand, offering great potential for positron emission computed tomography (PET) imaging of CXCR4 expression. This study reports the preparation and evaluation of ( 64 Cu)-radiolabeled ubiquitin for CXCR4 imaging. The ubiquitin was first fused with a C-terminal GGCGG sequence, and the resulting recombinant ubiquitin derivative UbCG4 was then functionalized with the trans -cyclooctene (TCO) moiety via thiol-maleimide click reaction, followed by 64 Cu-radiolabeling through the TCO/Tz (tetrazine)-based Diels-Alder click reaction. In the prepared in vitro studies, the prepared ( 64 Cu)-UbCG4 showed significantly higher specific uptakes in the 4T1 breast cancer cells compared with the uptakes in the CXCR4-knockdown 4T1 cells. In the in vivo evaluation in the 4T1-xenograft mouse model, ( 64 Cu)-UbCG4 demonstrated a similar tumor uptake but much lower backgrounds compared with 64 Cu-labeled AMD3465. These results suggested that ( 64 Cu)-UbCG4 could serve as a potent PET tracer for the noninvasive imaging of CXCR4 expression in tumors.
Competing Interests: The authors declare no competing financial interest.
Databáze: MEDLINE