89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma
Abstract [177Lu]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...
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| Format: | Article |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10139-6 |
| _version_ | 1818022530467758080 |
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| author | Danique Giesen Marjolijn N. Lub-de Hooge Marcel Nijland Helen Heyerdahl Jostein Dahle Elisabeth G. E. de Vries Martin Pool |
| author_facet | Danique Giesen Marjolijn N. Lub-de Hooge Marcel Nijland Helen Heyerdahl Jostein Dahle Elisabeth G. E. de Vries Martin Pool |
| author_sort | Danique Giesen |
| collection | DOAJ |
| description | Abstract [177Lu]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 89Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [177Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with 89Zr. [89Zr]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 [89Zr]Zr-N-sucDf-NNV003 and [177Lu]Lu-DOTA-NNV003 RIT were compared. [89Zr]Zr-N-sucDf-NNV003 accumulated in REC1 tumors over time, which was not observed for non-specific, 111In-labeled IgG control molecule. In RAMOS tumor-bearing mice, [89Zr]Zr-N-sucDf-NNV003 tumor uptake was higher than [111In]In-DTPA-IgG at all tested tracer protein doses (10 µg, 25 µg and 100 µg; P < 0.01), further confirming [89Zr]Zr-N-sucDf-NNV003 tumor uptake is CD37-mediated. [89Zr]Zr-N-sucDf-NNV003 and [177Lu]Lu-DOTA-NNV003 RIT showed similar ex vivo biodistribution and tumor uptake in the RAMOS tumor model. In conclusion, [89Zr]Zr-N-sucDf-NNV003 PET imaging can serve to accurately predict CD37-targeting of [177Lu]Lu-DOTA-NNV003. To enable clinical implementation, we established a good manufacturing practice (GMP)-compliant production process for [89Zr]Zr-N-sucDf-NNV003. |
| first_indexed | 2024-12-10T03:29:53Z |
| format | Article |
| id | doaj.art-27fc17b8666243629d517ab3e7966443 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T03:29:53Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-27fc17b8666243629d517ab3e79664432022-12-22T02:03:51ZengNature PortfolioScientific Reports2045-23222022-04-0112111010.1038/s41598-022-10139-689Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphomaDanique Giesen0Marjolijn N. Lub-de Hooge1Marcel Nijland2Helen Heyerdahl3Jostein Dahle4Elisabeth G. E. de Vries5Martin Pool6Department of Medical Oncology, University Medical Center GroningenDepartment of Clinical Pharmacy and Pharmacology, University Medical Center GroningenDepartment of Hematology, University Medical Center GroningenNordic Nanovector ASANordic Nanovector ASADepartment of Medical Oncology, University Medical Center GroningenDepartment of Medical Oncology, University Medical Center GroningenAbstract [177Lu]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 89Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [177Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with 89Zr. [89Zr]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 [89Zr]Zr-N-sucDf-NNV003 and [177Lu]Lu-DOTA-NNV003 RIT were compared. [89Zr]Zr-N-sucDf-NNV003 accumulated in REC1 tumors over time, which was not observed for non-specific, 111In-labeled IgG control molecule. In RAMOS tumor-bearing mice, [89Zr]Zr-N-sucDf-NNV003 tumor uptake was higher than [111In]In-DTPA-IgG at all tested tracer protein doses (10 µg, 25 µg and 100 µg; P < 0.01), further confirming [89Zr]Zr-N-sucDf-NNV003 tumor uptake is CD37-mediated. [89Zr]Zr-N-sucDf-NNV003 and [177Lu]Lu-DOTA-NNV003 RIT showed similar ex vivo biodistribution and tumor uptake in the RAMOS tumor model. In conclusion, [89Zr]Zr-N-sucDf-NNV003 PET imaging can serve to accurately predict CD37-targeting of [177Lu]Lu-DOTA-NNV003. To enable clinical implementation, we established a good manufacturing practice (GMP)-compliant production process for [89Zr]Zr-N-sucDf-NNV003.https://doi.org/10.1038/s41598-022-10139-6 |
| spellingShingle | Danique Giesen Marjolijn N. Lub-de Hooge Marcel Nijland Helen Heyerdahl Jostein Dahle Elisabeth G. E. de Vries Martin Pool 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma Scientific Reports |
| title | 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma |
| title_full | 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma |
| title_fullStr | 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma |
| title_full_unstemmed | 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma |
| title_short | 89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma |
| title_sort | 89zr pet imaging to predict tumor uptake of 177lu nnv003 anti cd37 radioimmunotherapy in mouse models of b cell lymphoma |
| url | https://doi.org/10.1038/s41598-022-10139-6 |
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