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

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