Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography
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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.
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.
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.
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.
KeywordsImmuno-PET Radioimmunotherapy Ibritumomab tiuxetan Zirconium-89 Yttrium-90
This project was financially supported by the Dutch Technology Foundation (STW, grant VBC.6120). The authors thank Schering Nederland BV (The Netherlands) for supply of Zevalin and for reviewing the manuscript, the technical staff of BV Cyclotron and the Radionuclide Centre for supply and processing of 89Zr, Jan H. Rector (Solid State Physics, VU university) for sputtering 89Y on copper supports, Adriaan A. Lammertsma for providing PET imaging facilities, and Yvonne W.S. Jauw and Ronald Boellaard for performing PET reconstructions.
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