|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ИНХС РАН |
||
Engineered modular recombinant transporters: Application of new platform for targeted radiotherapeutic agents to alpha-particle emitting At-211статья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus,
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Rosenkranz Andrey A., Vaidyanathan Ganesan, Pozzi Oscar R., Lunin Vladimir G., Zalutsky Michael R., Sobolev Alexander S.
- Журнал: International Journal of Radiation Oncology Biology Physics
- Том: 72
- Номер: 1
- Год издания: 2008
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 193
- Последняя страница: 200
- DOI: 10.1016/j.ijrobp.2008.05.055
- Аннотация: Purpose: To generate and evaluate a modular recombinant transporter (MRT) for targeting At-211 to cancer cells overexpressing the epidermal growth factor receptor (EGFR). Methods and Materials: The MRT was produced with four functional modules: (1) human epidermal growth factor as the internalizable ligand, (2) the optimized nuclear localization sequence of simian vacuolating virus 40 (SV40) large T-antigen, (3) a translocation domain of diphtheria toxin as an endosomolytic module, and (4) the Escherichia coli hem oglobin-like protein (HMP) as a carrier module. MRT was labeled using N-succinimidyl 3-[At-211]astato-5-guanidinomethylbenzoate (SAGMB), its I-125 analogue SGMIB, or with I-131 using Iodogen. Binding, internalization, and clonogenic assays were performed with EGFR-expressing A431, D247 MG, and U87MG.wtEGFR human cancer cell lines. Results: The affinity of SGMIB-MRT binding to A431 cells, determined by Scatchard analysis, was 22 nM, comparable to that measured before labeling. The binding of SGMIB-MRT and its internalization by A431 cancer cells was 96% and 99% EGFR specific, respectively. Paired label assays demonstrated that compared with Iodogen-labeled MRT, SGMIB-MRT and SAGMB-MRT exhibited more than threefold greater peak levels and durations of intracellular retention of activity. SAGMB-MRT was 10-20 times more cytotoxic than [At-211]astatide for all three cell lines. Conclusion: The results of this study have demonstrated the initial proof of principle for the MRT approach for designing targeted a-particle emitting radiotherapeutic agents. The high cytotoxicity of SAGMB-MRT for cancer cells overexpressing EGFR suggests that this At-211-labeled conjugate has promise for the treatment of malignancies such as glioma, which overexpress this receptor. (C) 2008 Elsevier Inc.
- Добавил в систему: Розенкранц Андрей Александрович