Send to

Choose Destination
ACS Omega. 2019 Jul 22;4(7):12432-12437. doi: 10.1021/acsomega.9b00678. eCollection 2019 Jul 31.

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

Li H1,2, Zhang X2, Wu HY3, Sun L2,4, Ma Y2,4, Xu J1, Lin Q3, Zeng D2,4.

Author information

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.
Department of Chemistry, State University of New York at Buffalo, 679 Natural Sciences Complex, Buffalo, New York 14260, United States.
Department of Diagnostic Radiology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., CRR210B, Portland, Oregon 97239, United States.


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 (64Cu)-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 64Cu-radiolabeling through the TCO/Tz (tetrazine)-based Diels-Alder click reaction. In the prepared in vitro studies, the prepared (64Cu)-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, (64Cu)-UbCG4 demonstrated a similar tumor uptake but much lower backgrounds compared with 64Cu-labeled AMD3465. These results suggested that (64Cu)-UbCG4 could serve as a potent PET tracer for the noninvasive imaging of CXCR4 expression in tumors.

Conflict of interest statement

The authors declare no competing financial interest.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center