Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography

Lars R. Perk, Otto J. Visser, M. Stigter-Van Walsum, Maria J W D Vosjan, Gerard W M Visser, Josée M. Zijlstra, Peter C. Huijgens, Guus A M S Van Dongen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: To evaluate whether 89Zr can be used as a PET surrogate label for quantification of 90Y-ibritumomab tiuxetan ( 90Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy. Methods: Zevalin was labelled with 89Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of 89Zr-Zevalin and 88Y-Zevalin (as a substitute for 90Y), samples were incubated in human serum at 37°C up to 6 days. Biodistribution of 89Zr-Zevalin and 88Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin's lymphoma (NHL) xenograft line Ramos. The clinical performance of 89Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [18F]FDG-PET 2 weeks previously. Results: Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83±0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of 89Zr-Zevalin always exceeded 95% and 80%, respectively. 89Zr-Zevalin showed the same stability in serum as 88Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected 89Zr-Zevalin and 88Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for 89Zr than for 88Y. PET images obtained after injection of 89Zr-Zevalin showed clear targeting of all known tumour lesions. Conclusion: 89Zr-Zevalin and 88Y-Zevalin showed a very similar biodistribution in mice, implying that 89Zr-Zevalin-PET might be well suited for prediction of 90Y-Zevalin biodistribution in a myeloablative setting.

Original languageEnglish
Pages (from-to)1337-1345
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume33
Issue number11
DOIs
Publication statusPublished - 1 Nov 2006

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