期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 32, 期 8, 页码 943-951出版社
SPRINGER
DOI: 10.1007/s00259-005-1798-8
关键词
I-131-rituximab; repeated injections; biodistribution; pharmacokinetics
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 I-131-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/m(2)) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq I-131-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 I-131-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 T-1/2 beta, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T-1/2 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 I-131-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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