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Published in: Journal of Neuro-Oncology 3/2019

01-05-2019 | Medulloblastoma | Laboratory Investigation

Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI

Authors: Bridget A. Kennis, Keith A. Michel, William B. Brugmann, Alvaro Laureano, Rong-Hua Tao, Srinivas S. Somanchi, Samuel A. Einstein, Javiera B. Bravo-Alegria, Shinji Maegawa, Andrew Wahba, Simin Kiany, Nancy Gordon, Lucia Silla, Dawid Schellingerhout, Soumen Khatua, Wafik Zaky, David Sandberg, Laurence Cooper, Dean A. Lee, James A. Bankson, Vidya Gopalakrishnan

Published in: Journal of Neuro-Oncology | Issue 3/2019

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Abstract

Purpose

Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent studies have shown the ability of natural killer (NK) cells to lyse MB cell lines in vitro, but in vivo successes remain elusive and the efficacy and fate of NK cells in vivo remain unknown.

Methods

To address these questions, we injected MB cells into the cerebellum of immunodeficient mice and examined tumor growth at various days after tumor establishment via bioluminescence imaging. NK cells were labeled with a fluorine-19 (19F) MRI probe and subsequently injected either intratumorally or contralaterally to the tumor in the cerebellum and effect on tumor growth was monitored.

Results

The 19F probe efficiently labeled the NK cells and exhibited little cytotoxicity. Fluorine-19 MRI confirmed the successful and accurate delivery of the labeled NK cells to the cerebellum of the mice. Administration of 19F–labeled NK cells suppressed MB growth, with the same efficacy as unlabeled cells. Immunohistochemistry confirmed the presence of NK cells within the tumor, which was associated with induction of apoptosis in tumor cells. NK cell migration to the tumor from a distal location as well as activation of apoptosis was also demonstrated by immunohstochemistry.

Conclusions

Our results show that NK cells present a novel opportunity for new strategies in MB treatment. Further, 19F-labeled NK cells can suppress MB growth while enabling 19F MRI to provide imaging feedback that can facilitate study and optimization of therapeutic paradigms.
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Metadata
Title
Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI
Authors
Bridget A. Kennis
Keith A. Michel
William B. Brugmann
Alvaro Laureano
Rong-Hua Tao
Srinivas S. Somanchi
Samuel A. Einstein
Javiera B. Bravo-Alegria
Shinji Maegawa
Andrew Wahba
Simin Kiany
Nancy Gordon
Lucia Silla
Dawid Schellingerhout
Soumen Khatua
Wafik Zaky
David Sandberg
Laurence Cooper
Dean A. Lee
James A. Bankson
Vidya Gopalakrishnan
Publication date
01-05-2019
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-019-03091-5

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