Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.
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.
['Kennis|Bridget A|BA|', 'Michel|Keith A|KA|', 'Brugmann|William B|WB|', 'Laureano|Alvaro|A|', 'Tao|Rong-Hua|RH|', 'Somanchi|Srinivas S|SS|', 'Einstein|Samuel A|SA|', 'Bravo-Alegria|Javiera B|JB|', 'Maegawa|Shinji|S|', 'Wahba|Andrew|A|', 'Kiany|Simin|S|', 'Gordon|Nancy|N|', 'Silla|Lucia|L|', 'Schellingerhout|Dawid|D|', 'Khatua|Soumen|S|', 'Zaky|Wafik|W|', 'Sandberg|David|D|', 'Cooper|Laurence|L|', 'Lee|Dean A|DA|', 'Bankson|James A|JA|', 'Gopalakrishnan|Vidya|V|http://orcid.org/0000-0002-4448-4698']
D000818:Animals D017209:Apoptosis D049109:Cell Proliferation D002528:Cerebellar Neoplasms D016903:Drug Monitoring D005462:Fluorine Radioisotopes D006801:Humans D007694:Killer Cells, Natural D008279:Magnetic Resonance Imaging D008527:Medulloblastoma D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
Fluorine-19 MRI Medulloblastoma Immunotherapy NK-cell delivery