Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy

Autor: Hiroki Kato, Xuhao Huang, Yuichiro Kadonaga, Daisuke Katayama, Kazuhiro Ooe, Atsushi Shimoyama, Kazuya Kabayama, Atsushi Toyoshima, Atsushi Shinohara, Jun Hatazawa, Koichi Fukase
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-12 (2021)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-021-00963-9
Popis: Abstract Background 211At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of 211At-labeled gold nanoparticles (211At-AuNP) administered intratumorally. Results AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with 211At (211At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. 211At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, 211At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of 211At. Tumor growth was strongly suppressed for both C6 and PANC-1 by 211At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with 211At-AuNP-S-mPEG with a diameter of 5 nm. Conclusions The intratumoral single administration of a simple nanoparticle, 211At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide. Graphic Abstract
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