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Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated 131I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin’s lymphoma (NHL).

Methods

Patients received standard weekly therapy with rituximab (375 mg/m2) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq 131I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post 131I-rituximab injection prior to the second and third injections, respectively.

Results

A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T1/2β, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T1/2 of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48–0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver.

Conclusion

These results show that the biodistribution and tissue kinetics of 131I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.

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Acknowledgements

We thankfully acknowledge support from the Swiss Cancer League No KFS 991-02-2000 and excellent technical assistance from the staff of the Nuclear Medicine Department.

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Authors and Affiliations

  1. Service of Nuclear Medicine, University Hospital of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland

    Cristian Antonescu, Angelika Bischof Delaloye, Marek Kosinski, Andreas O. Schaffland, Carine Grannavel & Franz Buchegger

  2. Institute of Applied Radiophysics, University of Lausanne, Lausanne, Switzerland

    Marek Kosinski, Pascal Monnin & Francis R. Verdun

  3. Multidisciplinary Oncology Center, University Hospital of Lausanne, Lausanne, Switzerland

    Nicolas Ketterer

  4. Center for Hematological Malignancies, Oregon Health and Science University, Portland, OR, USA

    Tibor Kovacsovics

  5. Service of Nuclear Medicine, University Hospital of Geneva, Geneva, Switzerland

    Franz Buchegger

Authors
  1. Cristian Antonescu
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  2. Angelika Bischof Delaloye
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  3. Marek Kosinski
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  7. Carine Grannavel
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  9. Francis R. Verdun
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  10. Franz Buchegger
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Correspondence to Franz Buchegger.

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Antonescu, C., Bischof Delaloye, A., Kosinski, M. et al. Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics. Eur J Nucl Med Mol Imaging 32, 943–951 (2005). https://doi.org/10.1007/s00259-005-1798-8

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  • DOI: https://doi.org/10.1007/s00259-005-1798-8

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