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In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.
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Zhang H, Wu Y, Wang J, Tang Z, Ren Y, Ni D, Gao H, Song R, Jin T, Li Q, Bu W, Yao Z,


Zhang H, Wu Y, Wang J, Tang Z, Ren Y, Ni D, Gao H, Song R, Jin T, Li Q, Bu W, Yao Z, (click to view)

Zhang H, Wu Y, Wang J, Tang Z, Ren Y, Ni D, Gao H, Song R, Jin T, Li Q, Bu W, Yao Z,

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Small (Weinheim an der Bergstrasse, Germany) 2017 11 23() doi 10.1002/smll.201702951

Abstract

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm(-1) s(-1) ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 10(7) labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.

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