In-Vivo Detection and Tracking of T Cells in Various Organs in a Melanoma Tumor Model by 19F-Fluorine MRS/MRI.

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Download: journal.pone.0164557.PDF (2100.07 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_1C2672B725FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In-Vivo Detection and Tracking of T Cells in Various Organs in a Melanoma Tumor Model by 19F-Fluorine MRS/MRI.
Journal
PloS one
Author(s)
Gonzales C., Yoshihara H.A., Dilek N., Leignadier J., Irving M., Mieville P., Helm L., Michielin O., Schwitter J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
11
Number
10
Pages
e0164557
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
19F-MRI and 19F-MRS can identify specific cell types after in-vitro or in-vivo 19F-labeling. Knowledge on the potential to track in-vitro 19F-labeled immune cells in tumor models by 19F-MRI/MRS is scarce.
To study 19F-based MR techniques for in-vivo tracking of adoptively transferred immune cells after in-vitro 19F-labeling, i.e. to detect and monitor their migration non-invasively in melanoma-bearing mice.
Splenocytes (SP) were labeled in-vitro with a perfluorocarbon (PFC) and IV-injected into non-tumor bearing mice. In-vitro PFC-labeled ovalbumin (OVA)-specific T cells from the T cell receptor-transgenic line OT-1, activated with anti-CD3 and anti-CD28 antibodies (Tact) or OVA-peptide pulsed antigen presenting cells (TOVA-act), were injected into B16 OVA melanoma-bearing mice. The distribution of the 19F-labelled donor cells was determined in-vivo by 19F-MRI/MRS. In-vivo 19F-MRI/MRS results were confirmed by ex-vivo 19F-NMR and flow cytometry.
SP, Tact, and TOVA-act were successfully PFC-labeled in-vitro yielding 3x1011-1.4x1012 19F-atoms/cell in the 3 groups. Adoptively transferred 19F-labeled SP, TOVA-act, and Tact were detected by coil-localized 19F-MRS in the chest, abdomen, and left flank in most animals (corresponding to lungs, livers, and spleens, respectively, with highest signal-to-noise for SP vs TOVA-act and Tact, p<0.009 for both). SP and Tact were successfully imaged by 19F-MRI (n = 3; liver). These in-vivo data were confirmed by ex-vivo high-resolution 19F-NMR-spectroscopy. By flow cytometric analysis, however, TOVA-act tended to be more abundant versus SP and Tact (liver: p = 0.1313; lungs: p = 0.1073; spleen: p = 0.109). Unlike 19F-MRI/MRS, flow cytometry also identified transferred immune cells (SP, Tact, and TOVA-act) in the tumors.
SP, Tact, and TOVA-act were successfully PFC-labeled in-vitro and detected in-vivo by non-invasive 19F-MRS/MRI in liver, lung, and spleen. The portion of 19F-labeled T cells in the adoptively transferred cell populations was insufficient for 19F-MRS/MRI detection in the tumor. While OVA-peptide-activated T cells (TOVA-act) showed highest infiltration into all organs, SP were detected more reliably by 19F-MRS/MRI, most likely explained by cell division of TOVA-act after injection, which dilutes the 19F content in the T cell-infiltrated organs. Non-dividing 19F-labeled cell species appear most promising to be tracked by 19F-MRS/MRI.

Keywords
Adoptive Transfer, Animals, Cell Line, Tumor, Cell Tracking/methods, Fluorine-19 Magnetic Resonance Imaging/methods, Fluorocarbons/metabolism, Liver/diagnostic imaging, Liver/immunology, Lung/diagnostic imaging, Lung/immunology, Magnetic Resonance Spectroscopy/methods, Melanoma, Experimental/diagnostic imaging, Melanoma, Experimental/immunology, Mice, Spleen/diagnostic imaging, Spleen/immunology, Staining and Labeling, T-Lymphocytes/metabolism, T-Lymphocytes/transplantation
Pubmed
Open Access
Yes
Create date
25/10/2016 18:17
Last modification date
20/08/2019 12:52
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