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

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.