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E. de Vries, which was made available to her institution (UMCG)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>[<jats:sup>177<\/jats:sup>Lu]Lu-DOTA-NNV003, a radioimmunoconjugate targeting CD37, is developed as novel radioimmunotherapy (RIT) treatment for patients with B cell non-Hodgkin\u2019s lymphoma (NHL). Since patients are at risk for developing hematological toxicities due to CD37 expression on normal B cells, we aimed to develop <jats:sup>89<\/jats:sup>Zr-labeled NNV003 for positron emission tomography (PET) imaging as a surrogate tool to predict [<jats:sup>177<\/jats:sup>Lu]Lu-DOTA-NNV003 RIT whole-body distribution and tumor uptake. NNV003 antibody was first radiolabeled with <jats:sup>89<\/jats:sup>Zr. [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 tumor uptake was evaluated by PET imaging of mice bearing human CD37-expressing REC1 B cell NHL or RAMOS Burkitt\u2019s lymphoma xenograft tumors followed by ex vivo analysis. Finally, CD37-targeting of [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 and [<jats:sup>177<\/jats:sup>Lu]Lu-DOTA-NNV003 RIT were compared. [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 accumulated in REC1 tumors over time, which was not observed for non-specific, <jats:sup>111<\/jats:sup>In-labeled IgG control molecule. In RAMOS tumor-bearing mice, [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 tumor uptake was higher than [<jats:sup>111<\/jats:sup>In]In-DTPA-IgG at all tested tracer protein doses (10\u00a0\u00b5g, 25\u00a0\u00b5g and 100\u00a0\u00b5g; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), further confirming [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 tumor uptake is CD37-mediated. [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 and [<jats:sup>177<\/jats:sup>Lu]Lu-DOTA-NNV003 RIT showed similar ex vivo biodistribution and tumor uptake in the RAMOS tumor model. In conclusion, [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003 PET imaging can serve to accurately predict CD37-targeting of [<jats:sup>177<\/jats:sup>Lu]Lu-DOTA-NNV003. To enable clinical implementation, we established a good manufacturing practice (GMP)-compliant production process for [<jats:sup>89<\/jats:sup>Zr]Zr-<jats:italic>N<\/jats:italic>-sucDf-NNV003.<\/jats:p>","DOI":"10.1038\/s41598-022-10139-6","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T14:02:45Z","timestamp":1650031365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["89Zr-PET imaging to predict tumor uptake of 177Lu-NNV003 anti-CD37 radioimmunotherapy in mouse models of B cell lymphoma"],"prefix":"10.1038","volume":"12","author":[{"given":"Danique","family":"Giesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolijn N. 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