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

Purpose: To evaluate whether Zr-89 can be used as a PET surrogate label for quantification of Y-90-ibritumomab tiuxetan (Y-90-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy. Methods: Zevalin was labelled with Zr-89 by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of Zr-89-Zevalin and Y-88-Zevalin ( as a substitute for Y-90), samples were incubated in human serum at 37 degrees C up to 6 days. Biodistribution of Zr-89-Zevalin and Y-88-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 Zr-89-Zevalin- PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [F-18] 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 Zr-89-Zevalin always exceeded 95% and 80%, respectively. Zr-89-Zevalin showed the same stability in serum as Y-88-Zevalin, with a radiochemical purity > 95% during a period of 6 days. The co-injected Zr-89-Zevalin and Y-88-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 Zr-89 than for Y-88. PET images obtained after injection of Zr-89-Zevalin showed clear targeting of all known tumour lesions. Conclusion: Zr-89-Zevalin and Y-88-Zevalin showed a very similar biodistribution in mice, implying that Zr-89-Zevalin-PET might be well suited for prediction of Y-90-Zevalin biodistribution in a myeloablative setting.