방사선의학 웹진

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Abstract

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.

Author information​

Kim EJ1,2, Kim BS1,3, Choi DB1, Chi SG2, Choi TH3.

11 Korea Drug Development Platform using Radio-Isotope (KDePRI), Korea Institute of Radiological and Medical Sciences , Seoul, Korea.

22 School of Life Sciences and Biotechnology, Korea University , Seoul, Korea.

33 Department of Molecular Imaging, Korea Institute of Radiological and Medical Sciences , Seoul, Korea.