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

Abstract

Purpose

To compare using immuno-PET/CT the distribution of ⁸⁹Zr-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 ⁹⁰Y-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 ⁸⁹Zr-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 ⁸⁹Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by ⁹⁰Y-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 ⁹⁰Y-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”.

Clinical Trial Application: CTA 2011-005474-38

Trial Registry: EudraCT

Electronic supplementary material

The online version of this article (doi:10.1007/s00259-015-3025-6) contains supplementary material, which is available to authorized users.