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Commun Biol. 2019 Feb 26;2:79. doi: 10.1038/s42003-019-0327-4. eCollection 2019.

90Y-NM600 targeted radionuclide therapy induces immunologic memory in syngeneic models of T-cell Non-Hodgkin's Lymphoma.

Author information

1
1Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI USA.
2
2Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI USA.
3
3Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI USA.
4
4Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI USA.
5
5University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI USA.

Abstract

Finding improved therapeutic strategies against T-cell Non-Hodgkin's Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with 86Y for positron emission tomography (PET) imaging and 90Y for targeted radionuclide therapy (TRT) of T-cell NHL. PET imaging and biodistribution performed in mouse models of T-cell NHL showed in vivo selective tumor uptake and retention of 86Y-NM600. An initial toxicity assessment examining complete blood counts, blood chemistry, and histopathology of major organs established 90Y-NM600 safety. Mice bearing T-cell NHL tumors treated with 90Y-NM600 experienced tumor growth inhibition, extended survival, and a high degree of cure with immune memory toward tumor reestablishment. 90Y-NM600 treatment was also effective against disseminated tumors, improving survival and cure rates. Finally, we observed a key role for the adaptive immune system in potentiating a durable anti-tumor response to TRT, especially in the presence of microscopic disease.

Conflict of interest statement

J.P.W. is a co-founder of Archeus Technologies, LLC, of which Z.S.M. is a member of the Scientific Advisory Board, and R.H. and J.J.G. are consultants. The remaining authors declare no competing interests.

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