Improved in Vivo Stability of Radioiodinated Rituximab Using an Iodination Linker for Radioimmunotherapy

Eun Jung Kim, Byoung Soo Kim, Dan Bee Choi, Sung-Gil Chi, Tae Hyun Choi

    Research output: Contribution to journalArticlepeer-review


    Purpose: Directly radioiodinated [131I]-rituximab has been developed as a radioimmunotherapeutic agent in patients with CD20-positive B cell non-Hodgkin's lymphoma. However, there are concerns over its in vivo catabolism and deiodination. A novel radioiodination linker, N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA), was synthesized for the preparation of stable radioiodinated proteins. Methods: The authors evaluated the potential of IBPA as a stable radioiodinated linker for rituximab. [125I]-IBPA was purified and conjugated with rituximab, and in vitro stability testing was performed in serum and liver microsomes. In vivo studies were performed after i.v. injection of [125I]-rituximab or [125I]-IBPA-rituximab to nude mice. Results: In in vitro studies, [125I]-IBPA-rituximab was stable in serum and liver microsomes. In static scans, high radioactivity was evident in the thyroid following injection of [125I]-rituximab, but low radioactivity was seen in the thyroid following injection of [125I]-IBPA-rituximab. In biodistribution studies, radioactivity uptake in thyroid glands of [125I]-IBPA-rituximab was decreased by approximately sevenfold compared to [125I]-rituximab. In pharmacokinetics, the half-life of [125I]-rituximab was shorter than that of [125I]-IBPA-rituximab in plasma of nude mice. Conclusions: The authors demonstrate that [125I]-IBPA-rituximab is more stable to metabolic deiodination in vivo than is [125I]-rituximab. Radioiodination of rituximab using IBPA is thus preferable to direct labeling in terms of in vivo stability.

    Original languageEnglish
    Pages (from-to)287-294
    Number of pages8
    JournalCancer Biotherapy and Radiopharmaceuticals
    Issue number8
    Publication statusPublished - 2016 Oct 1


    • CD20
    • deiodination
    • lymphoma
    • N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA)
    • radioimmunotherapy
    • rituximab

    ASJC Scopus subject areas

    • Oncology
    • Radiology Nuclear Medicine and imaging
    • Pharmacology
    • Cancer Research


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