I. HIGHLIGHTS OF THE YEARRIKEN Accel. Prog. Rep. 55 (2022)

RIKEN Accel. Prog. Rep. 55 (2022)

Intratumoral administration of astatine-211-labeled gold nanoparticle
for alpha therapy†
H. Kato,∗1 X. Huang,∗2 Y. Kadonaga,∗3 D. Katayama,∗1 K. Ooe,∗1 A. Shimoyama,∗2 K. Kabayama,∗2A. Toyoshima,∗3 A. Shinohara,∗3 J. Hatazawa,∗4 and K. Fukase∗2,∗3
As a local radiation therapy for cancer and in addition to external irradiation with γ-rays or X-rays,
the eﬀectiveness of brachytherapy using a sealed Xray source for prostate cancer, breast cancer, uterinecancer, head and neck cancer, and brain tumors iswell known. However, the invasiveness of the procedure, extra-lesion displacement of the sealed radiation
source, or adverse eﬀects caused by the leakage of Xrays from radionuclides with a long half-life into adjacent organs are problematic issues. α-ray-emitting nuclides have a high linear energy transfer (LET) and relative biological eﬀectiveness and are particularly toxic
to proliferating cells. Because of the short range of
α-ray emitters, normal tissues are minimally exposed
if the radiation sources are appropriately distributed.
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 useof nuclear fuel material.

Fig. 2. The radioactivity distributions at 4, 19, and 42
hours after the administration of 211 At-AuNP-S-mPEG
are shown. Strong radioactivity was found at the transplanted tumor sites. No systemic accumulation of radioactivity was observed in any of the organs.

The objective of this study was to propose an eﬀective nanoseed brachytherapy with signiﬁcantly reduced
radiation exposure. In the present study, we investigated the systemic and intratumoral distributions andveriﬁed the antitumor eﬀect of 211 At-labeled AuNP administered intratumorally (Fig. 1).
AuNP with a diameter of 5, 13, 30, or 120 nm
that had been modiﬁed with poly (ethylene glycol)

Fig. 1. 211 At-labeled gold nanoparticles administered intratumorally. α-ray caused DNA double-strand breakand kill the malignant cells.
†∗1
∗2
∗3
∗4

Condensed from the article in J. Nanobiotechnology 19, 223(2021)
Department of Nuclear Medicine and Tracer Kinetics, Osaka
University Graduate School of Medicine
Department of Chemistry, Graduate School of Science, Osaka University
Division of Science, Institute for Radiation Sciences, Osaka
University
Research Center for Nuclear Physics, Osaka University- S26 -Fig. 3. Changes in the tumor volumes of the C6 glial cells
after intratumoral administration (1.4±0.4 MBq/tumor
for rats). The C6 gliomas treated with the 5 nm particles had the lowest growth rate, based on tumor size.

1

I. HIGHLIGHTS OF THE YEARRIKEN Accel. Prog. Rep. 55 (2022)

methyl ether (mPEG) thiol and labeled with 211 At(211 At-AuNP-S-mPEG) were intratumorally administered to C6 glioma subcutaneously transplanted intorodent models. A part of 211 At used in this work
was produced in the 209 Bi(α, 2n)211 At reaction using
the RIKEN AVF cyclotron. 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(Fig. 2). Tumor growth was strongly suppressed by211
At-AuNP-S-mPEG without any critical side eﬀects.
In the C6 glioma model, the strongest antitumor eﬀect
was observed in the group treated with 211 At-AuNPS-mPEG with the smallest diameter of 5 nm (Fig. 3).
The intratumoral single administration of a simple nanoparticle, 211 At-AuNP-S-mPEG, was shown tosuppress 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.

2- S27 -