Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy
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 biodis...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-07-01
|
Series: | Journal of Nanobiotechnology |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12951-021-00963-9 |
id |
doaj-6c774306ce0d4817af2fa2f2c28fe432 |
---|---|
record_format |
Article |
spelling |
doaj-6c774306ce0d4817af2fa2f2c28fe4322021-08-01T11:32:26ZengBMCJournal of Nanobiotechnology1477-31552021-07-0119111210.1186/s12951-021-00963-9Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapyHiroki Kato0Xuhao Huang1Yuichiro Kadonaga2Daisuke Katayama3Kazuhiro Ooe4Atsushi Shimoyama5Kazuya Kabayama6Atsushi Toyoshima7Atsushi Shinohara8Jun Hatazawa9Koichi Fukase10Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of MedicineDepartment of Chemistry, Graduate School of Science, Osaka UniversityDivision of Science, Institute for Radiation Sciences, Osaka UniversityDepartment of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of MedicineDepartment of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of MedicineDepartment of Chemistry, Graduate School of Science, Osaka UniversityDepartment of Chemistry, Graduate School of Science, Osaka UniversityDivision of Science, Institute for Radiation Sciences, Osaka UniversityDepartment of Chemistry, Graduate School of Science, Osaka UniversityResearch Center for Nuclear Physics, Osaka UniversityDepartment of Chemistry, Graduate School of Science, Osaka UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-021-00963-9Astatine-211Alpha emittersGold nanoparticlesRadiolabelingCancer therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroki Kato Xuhao Huang Yuichiro Kadonaga Daisuke Katayama Kazuhiro Ooe Atsushi Shimoyama Kazuya Kabayama Atsushi Toyoshima Atsushi Shinohara Jun Hatazawa Koichi Fukase |
spellingShingle |
Hiroki Kato Xuhao Huang Yuichiro Kadonaga Daisuke Katayama Kazuhiro Ooe Atsushi Shimoyama Kazuya Kabayama Atsushi Toyoshima Atsushi Shinohara Jun Hatazawa Koichi Fukase Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy Journal of Nanobiotechnology Astatine-211 Alpha emitters Gold nanoparticles Radiolabeling Cancer therapy |
author_facet |
Hiroki Kato Xuhao Huang Yuichiro Kadonaga Daisuke Katayama Kazuhiro Ooe Atsushi Shimoyama Kazuya Kabayama Atsushi Toyoshima Atsushi Shinohara Jun Hatazawa Koichi Fukase |
author_sort |
Hiroki Kato |
title |
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_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_sort |
intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy |
publisher |
BMC |
series |
Journal of Nanobiotechnology |
issn |
1477-3155 |
publishDate |
2021-07-01 |
description |
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 |
topic |
Astatine-211 Alpha emitters Gold nanoparticles Radiolabeling Cancer therapy |
url |
https://doi.org/10.1186/s12951-021-00963-9 |
work_keys_str_mv |
AT hirokikato intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT xuhaohuang intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT yuichirokadonaga intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT daisukekatayama intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT kazuhiroooe intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT atsushishimoyama intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT kazuyakabayama intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT atsushitoyoshima intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT atsushishinohara intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT junhatazawa intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy AT koichifukase intratumoraladministrationofastatine211labeledgoldnanoparticleforalphatherapy |
_version_ |
1721245779869302784 |