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

Background F-19-MRI and F-19-MRS can identify specific cell types after in-vitro or in-vivo F-19-labeling. Knowledge on the potential to track in-vitro F-19-labeled immune cells in tumor models by F-19-MRI/MRS is scarce. Aim To study F-19-based MR techniques for in-vivo tracking of adoptively transferred immune cells after in-vitro F-19-labeling, i.e. to detect and monitor their migration non-invasively in melanoma-bearing mice. Methods 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 (T-act) or OVA-peptide pulsed antigen presenting cells (TOVA-act), were injected into B16 OVA melanoma- bearing mice. The distribution of the F-19-labelled donor cells was determined invivo by F-19-MRI/MRS. In-vivo F-19-MRI/MRS results were confirmed by ex-vivo F-19-NMR and flow cytometry. Results SP, T-act, and TOVA-act were successfully PFC-labeled in-vitro yielding 3x10(11)-1.4x10(12) F-19-atoms/cell in the 3 groups. Adoptively transferred F-19-labeled SP, TOVA-act, and T-act were detected by coil-localized F-19-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 T-act, p<0.009 for both). SP and T-act were successfully imaged by F-19-MRI (n = 3; liver). These in-vivo data were confirmed by ex-vivo high-resolution F-19-NMR-spectroscopy. By flow cytometric analysis, however, TOVA-act tended to be more abundant versus SP and T-act (liver: p = 0.1313; lungs: p = 0.1073; spleen: p = 0.109). Unlike F-19-MRI/MRS, flow cytometry also identified transferred immune cells (SP, T-act, and TOVA-act) in the tumors. Conclusion SP, T-act, and TOVA-act were successfully PFC-labeled in-vitro and detected in-vivo by noninvasive F-19-MRS/MRI in liver, lung, and spleen. The portion of F-19-labeled T cells in the adoptively transferred cell populations was insufficient for F-19-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 F-19-MRS/MRI, most likely explained by cell division of TOVA-act after injection, which dilutes the F-19 content in the T cell-infiltrated organs. Non-dividing F-19-labeled cell species appear most promising to be tracked by F-19-MRS/MRI.


Published in:
Plos One, 11, 10, e0164557
Year:
2016
Publisher:
San Francisco, Public Library of Science
ISSN:
1932-6203
Laboratories:


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 Record created 2017-01-24, last modified 2018-09-13

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