Tumour targeting and radiation dose of radioimmunotherapy with 90Y-rituximab in CD20+B-cell lymphoma as predicted by 89Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

Purpose To compare using immuno-PET/CT the distribution of Zr-89-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with Y-90-labelled rituximab in CD20+ B-cell lymphoma. Methods Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline Zr-89-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m(2)) of unlabelled rituximab followed by injection of Zr-89-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by Y-90-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. Results With a cold rituximab preload, the calculated whole-body dose of Y-90-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Conclusion Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the "prerituximab era".