Journal of Neuro-Oncology

, Volume 142, Issue 3, pp 395–407 | Cite as

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

  • 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. LeeEmail author
  • James A. BanksonEmail author
  • Vidya GopalakrishnanEmail author
Laboratory Investigation



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.


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.


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.


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.


Medulloblastoma NK-cell delivery Immunotherapy Fluorine-19 MRI 



This work was supported by funding support from Addis Faith Foundation, Noah’s Light Foundation, American Cancer Society Award Number 118165-RSG-09-273-01-DDC and the Rally Foundation for Childhood Cancers to VG.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human and animal participants

All animal experiments were approved by Institutional Animal Care and Use Committee (IACUC).

Supplementary material

11060_2019_3091_MOESM1_ESM.pdf (177 kb)
Supplementary material 1 (PDF 177 KB)
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Supplementary material 2 (PDF 102510 KB)
11060_2019_3091_MOESM3_ESM.pdf (246 kb)
Supplementary material 3 (PDF 246 KB)
11060_2019_3091_MOESM4_ESM.pdf (106 kb)
Supplementary material 4 (PDF 105 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
Corrected Publication 2019

Authors and Affiliations

  • Bridget A. Kennis
    • 1
  • Keith A. Michel
    • 2
  • William B. Brugmann
    • 1
  • Alvaro Laureano
    • 1
    • 4
  • Rong-Hua Tao
    • 1
  • Srinivas S. Somanchi
    • 1
  • Samuel A. Einstein
    • 2
  • Javiera B. Bravo-Alegria
    • 1
  • Shinji Maegawa
    • 1
  • Andrew Wahba
    • 1
  • Simin Kiany
    • 1
  • Nancy Gordon
    • 1
  • Lucia Silla
    • 4
  • Dawid Schellingerhout
    • 3
  • Soumen Khatua
    • 1
  • Wafik Zaky
    • 1
  • David Sandberg
    • 1
    • 6
  • Laurence Cooper
    • 1
    • 5
  • Dean A. Lee
    • 1
    • 7
    Email author
  • James A. Bankson
    • 2
    • 9
    Email author
  • Vidya Gopalakrishnan
    • 1
    • 8
    Email author
  1. 1.Division of PediatricsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Imaging PhysicsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Diagnostic RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Division of Transplantation and Cellular Therapy, Hospital das Clinicas de Porto AlegreFederal University of Rio Grande do SulPorto AlegreBrazil
  5. 5.Ziopharm OncologyBostonUSA
  6. 6.Department of Pediatric NeurosurgeryUniversity of Texas Health Science CenterHoustonUSA
  7. 7.Department of PediatricsOhio State UniversityColumbusUSA
  8. 8.Division of PediatricsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.Department of Imaging PhysicsThe University of Texas MD Anderson Cancer CenterHoustonUSA

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