Biodrugs 2006; 20 (4): 201-207

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