Cargando…
Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy
BACKGROUND: (211)At 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 biodistribut...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317303/ https://www.ncbi.nlm.nih.gov/pubmed/34320997 http://dx.doi.org/10.1186/s12951-021-00963-9 |
_version_ | 1783730045529882624 |
---|---|
author | Kato, Hiroki Huang, Xuhao Kadonaga, Yuichiro Katayama, Daisuke Ooe, Kazuhiro Shimoyama, Atsushi Kabayama, Kazuya Toyoshima, Atsushi Shinohara, Atsushi Hatazawa, Jun Fukase, Koichi |
author_facet | Kato, Hiroki Huang, Xuhao Kadonaga, Yuichiro Katayama, Daisuke Ooe, Kazuhiro Shimoyama, Atsushi Kabayama, Kazuya Toyoshima, Atsushi Shinohara, Atsushi Hatazawa, Jun Fukase, Koichi |
author_sort | Kato, Hiroki |
collection | PubMed |
description | BACKGROUND: (211)At 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 (211)At-labeled gold nanoparticles ((211)At-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 (211)At ((211)At-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. (211)At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, (211)At-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 (211)At. Tumor growth was strongly suppressed for both C6 and PANC-1 by (211)At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with (211)At-AuNP-S-mPEG with a diameter of 5 nm. CONCLUSIONS: The intratumoral single administration of a simple nanoparticle, (211)At-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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00963-9. |
format | Online Article Text |
id | pubmed-8317303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83173032021-07-28 Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy Kato, Hiroki Huang, Xuhao Kadonaga, Yuichiro Katayama, Daisuke Ooe, Kazuhiro Shimoyama, Atsushi Kabayama, Kazuya Toyoshima, Atsushi Shinohara, Atsushi Hatazawa, Jun Fukase, Koichi J Nanobiotechnology Research BACKGROUND: (211)At 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 (211)At-labeled gold nanoparticles ((211)At-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 (211)At ((211)At-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. (211)At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, (211)At-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 (211)At. Tumor growth was strongly suppressed for both C6 and PANC-1 by (211)At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with (211)At-AuNP-S-mPEG with a diameter of 5 nm. CONCLUSIONS: The intratumoral single administration of a simple nanoparticle, (211)At-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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00963-9. BioMed Central 2021-07-28 /pmc/articles/PMC8317303/ /pubmed/34320997 http://dx.doi.org/10.1186/s12951-021-00963-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kato, Hiroki Huang, Xuhao Kadonaga, Yuichiro Katayama, Daisuke Ooe, Kazuhiro Shimoyama, Atsushi Kabayama, Kazuya Toyoshima, Atsushi Shinohara, Atsushi Hatazawa, Jun Fukase, Koichi Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title | Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title_full | Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title_fullStr | Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title_full_unstemmed | Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title_short | Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
title_sort | intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317303/ https://www.ncbi.nlm.nih.gov/pubmed/34320997 http://dx.doi.org/10.1186/s12951-021-00963-9 |
work_keys_str_mv | AT katohiroki intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT huangxuhao intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT kadonagayuichiro intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT katayamadaisuke intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT ooekazuhiro intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT shimoyamaatsushi intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT kabayamakazuya intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT toyoshimaatsushi intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT shinoharaatsushi intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT hatazawajun intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT fukasekoichi intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy |