Abundant Tyrosine Residues in the Antigen Binding Site in Anti-Osteosarcoma Monoclonal Antibodies Tp-1 and Tp-3: Application to radiolabeling

Olafsen, Tove; Bruland, Øyvind S.; Zalutsky, Michael R.; Sandlie, Inger

doi:10.3109/02841869609101644

Cited by 13 publications

(2 citation statements)

References 23 publications

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“…Tyrosine residues abound in the complementarity determining region (CDR) of antibodies ( 23 ). Iodination of tyrosine can considerably decrease or destroy the antigen-binding capability of mAbs ( 24 ). On the other hand, lysines are present in CDRs to a much lesser extent ( 25 ) and conjugation labeling provides better immunoreactivity of the conjugate and tumor accumulation.…”

Section: Discussionmentioning

confidence: 99%

Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor antibody using novel bifunctional iodination linker for radioimmunotherapy

Kim

Choi

et al. 2016

Oncology Reports

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Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target tumor cells. Radioiodine is most commonly employed to prepare radiolabeled proteins (antibodies, peptides) for in vitro and in vivo applications. A major shortcoming of radioiodinated proteins prepared by direct labeling methods is their deiodination in vivo. For the preparation of more stable radioiodinated antibodies, we developed a new linker (N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA). This study evaluated the usefulness of IBPA as a linker for the stable radioiodinated internalizing antibody, cetuximab. Directly labeled cetuximab ([125I]-cetuximab) was prepared by the chloramine T method. To prepare indirectly labeled cetuximab using IBPA ([125I]-IBPA-cetuximab), IBPA was radioiodinated using chloramine-T to give N-(4-isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-IBPA), which was purified by high performance liquid chromatography. [125I]-IBPA was then conjugated to cetuximab. In vitro target binding and internalizing assays were performed in PC9, LS174T, and FaDu cell lines. In vivo planar images were obtained using an Inveon SPECT scanner 3, 24, 48, and 168 h after i.v. injection of [125I]-cetuximab or [125I]-IBPA-cetuximab in athymic mice bearing LS174T tumor xenografts. Specific binding and internalized radioactivity of [125I]-IBPA-cetuximab were higher than those of [125I]-cetuximab in PC9, LS174T, and FaDu cell lines. In planar images scant radioactivity was evident in thyroid glands after injection of [125I]-IBPA-cetuximab, while a high level of radioactivity was present in thyroid glands after injection of [125I]-cetuximab. Tumor uptake value of [125I]-IBPA-cetuximab was higher than that of [125I]-cetuximab for up to 168 h. [125I]-IBPA-cetuximab is stable and resistant to deiodination in vivo. IBPA is a promising bi-functional linker for radioiodination of internalizing monoclonal antibodies for in vivo applications including radioimmunotherapy.

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Section: Discussionmentioning

confidence: 99%

Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor antibody using novel bifunctional iodination linker for radioimmunotherapy

Kim

Choi

et al. 2016

Oncology Reports

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show abstract

“…However, it does not have a defined antigen and thus far has somewhat limited clinical applications. 14,15 One approach that has been utilized is testing osteosarcoma tumor tissue for expression of surface receptors that have been developed for other therapeutic approaches. As an example trastuzumab, developed for human epidermal growth factor receptor-2 (HER2) overexpressing breast cancer, has been tested in clinical trials of osteosarcoma by the Children's Oncology Group based on HER2 expression being prognostic in a retrospective study …”

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confidence: 99%