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(89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma

[(177)Lu]Lu-DOTA-NNV003, a radioimmunoconjugate targeting CD37, is developed as novel radioimmunotherapy (RIT) treatment for patients with B cell non-Hodgkin’s lymphoma (NHL). Since patients are at risk for developing hematological toxicities due to CD37 expression on normal B cells, we aimed to dev...

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Autores principales: Giesen, Danique, Hooge, Marjolijn N. Lub-de, Nijland, Marcel, Heyerdahl, Helen, Dahle, Jostein, de Vries, Elisabeth G. E., Pool, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012778/
https://www.ncbi.nlm.nih.gov/pubmed/35428777
http://dx.doi.org/10.1038/s41598-022-10139-6
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author Giesen, Danique
Hooge, Marjolijn N. Lub-de
Nijland, Marcel
Heyerdahl, Helen
Dahle, Jostein
de Vries, Elisabeth G. E.
Pool, Martin
author_facet Giesen, Danique
Hooge, Marjolijn N. Lub-de
Nijland, Marcel
Heyerdahl, Helen
Dahle, Jostein
de Vries, Elisabeth G. E.
Pool, Martin
author_sort Giesen, Danique
collection PubMed
description [(177)Lu]Lu-DOTA-NNV003, a radioimmunoconjugate targeting CD37, is developed as novel radioimmunotherapy (RIT) treatment for patients with B cell non-Hodgkin’s lymphoma (NHL). Since patients are at risk for developing hematological toxicities due to CD37 expression on normal B cells, we aimed to develop (89)Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [(177)Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with (89)Zr. [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake was evaluated by PET imaging of mice bearing human CD37-expressing REC1 B cell NHL or RAMOS Burkitt’s lymphoma xenograft tumors followed by ex vivo analysis. Finally, CD37-targeting of [(89)Zr]Zr-N-sucDf-NNV003 and [(177)Lu]Lu-DOTA-NNV003 RIT were compared. [(89)Zr]Zr-N-sucDf-NNV003 accumulated in REC1 tumors over time, which was not observed for non-specific, (111)In-labeled IgG control molecule. In RAMOS tumor-bearing mice, [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake was higher than [(111)In]In-DTPA-IgG at all tested tracer protein doses (10 µg, 25 µg and 100 µg; P < 0.01), further confirming [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake is CD37-mediated. [(89)Zr]Zr-N-sucDf-NNV003 and [(177)Lu]Lu-DOTA-NNV003 RIT showed similar ex vivo biodistribution and tumor uptake in the RAMOS tumor model. In conclusion, [(89)Zr]Zr-N-sucDf-NNV003 PET imaging can serve to accurately predict CD37-targeting of [(177)Lu]Lu-DOTA-NNV003. To enable clinical implementation, we established a good manufacturing practice (GMP)-compliant production process for [(89)Zr]Zr-N-sucDf-NNV003.
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spelling pubmed-90127782022-04-18 (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma Giesen, Danique Hooge, Marjolijn N. Lub-de Nijland, Marcel Heyerdahl, Helen Dahle, Jostein de Vries, Elisabeth G. E. Pool, Martin Sci Rep Article [(177)Lu]Lu-DOTA-NNV003, a radioimmunoconjugate targeting CD37, is developed as novel radioimmunotherapy (RIT) treatment for patients with B cell non-Hodgkin’s lymphoma (NHL). Since patients are at risk for developing hematological toxicities due to CD37 expression on normal B cells, we aimed to develop (89)Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [(177)Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with (89)Zr. [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake was evaluated by PET imaging of mice bearing human CD37-expressing REC1 B cell NHL or RAMOS Burkitt’s lymphoma xenograft tumors followed by ex vivo analysis. Finally, CD37-targeting of [(89)Zr]Zr-N-sucDf-NNV003 and [(177)Lu]Lu-DOTA-NNV003 RIT were compared. [(89)Zr]Zr-N-sucDf-NNV003 accumulated in REC1 tumors over time, which was not observed for non-specific, (111)In-labeled IgG control molecule. In RAMOS tumor-bearing mice, [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake was higher than [(111)In]In-DTPA-IgG at all tested tracer protein doses (10 µg, 25 µg and 100 µg; P < 0.01), further confirming [(89)Zr]Zr-N-sucDf-NNV003 tumor uptake is CD37-mediated. [(89)Zr]Zr-N-sucDf-NNV003 and [(177)Lu]Lu-DOTA-NNV003 RIT showed similar ex vivo biodistribution and tumor uptake in the RAMOS tumor model. In conclusion, [(89)Zr]Zr-N-sucDf-NNV003 PET imaging can serve to accurately predict CD37-targeting of [(177)Lu]Lu-DOTA-NNV003. To enable clinical implementation, we established a good manufacturing practice (GMP)-compliant production process for [(89)Zr]Zr-N-sucDf-NNV003. Nature Publishing Group UK 2022-04-15 /pmc/articles/PMC9012778/ /pubmed/35428777 http://dx.doi.org/10.1038/s41598-022-10139-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Giesen, Danique
Hooge, Marjolijn N. Lub-de
Nijland, Marcel
Heyerdahl, Helen
Dahle, Jostein
de Vries, Elisabeth G. E.
Pool, Martin
(89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title_full (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title_fullStr (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title_full_unstemmed (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title_short (89)Zr-PET imaging to predict tumor uptake of (177)Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
title_sort (89)zr-pet imaging to predict tumor uptake of (177)lu-nnv003 anti-cd37 radioimmunotherapy in mouse models of b cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012778/
https://www.ncbi.nlm.nih.gov/pubmed/35428777
http://dx.doi.org/10.1038/s41598-022-10139-6
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