Ⅲ-3. Radiochemistry & Nuclear Chemistry
RIKEN
Accel. Prog. Rep. 56 (2023)

RIKEN Accel. Prog. Rep. 56 (2023)

Astatine-211-labeled gold nanoparticles for targeted alpha-particle
therapy via intravenous injection†
X. Huang,∗1 K. Kaneda-Nakashima,∗2,∗3 Y. Kadonaga,∗4 K. Kabayama,∗1,∗2,∗3 A. Shimoyama,∗1,∗2,∗3K. Ooe,∗2,∗3 H. Kato,∗4 A. Toyoshima,∗2,∗3 A. Shinohara,∗2,∗5 H. Haba,∗6 Y. Wang,∗6 and K. Fukase∗1,∗2,∗3†∗1∗2∗3∗4∗5∗6Condensed from the article in Pharmaceutics 14, 2705(2022)
Graduate School of Science, Osaka University
Institute for Radiation Sciences, Osaka University
Forefront Research Center, Osaka University
Graduate School of Medicine, Osaka University
Osaka Aoyama University
RIKEN Nishina Center- 155 -

5 nm 211 At-AuNPs@H16, and 5 nm 211 At-AuNPs@
H16/RGD), as shown in Fig. 1, can be labeled with211
At in a high RCY.

(a)

Active targeting nanoparticles(Tumor pH or receptor binding)

Passive targeting nanoparticles(EPR effect)

M. W. 6000

5 nm AuNPs@mPEG
RCY: 99%

10000

M. W. 2000
In 0.1M PBS pH 6.0

M. W. 6000

30 nm AuNPs@mPEG
RCY: 99%

5 nm AuNPs@H16
RCY: 92%(b)CTL(c)

54..01 MBq

3.5
Weight (g)1000

M. W. 2000
In 0.1M PBS pH 6.0

5 nm AuNPs@H16 /RGD
RCY: 93%

4.5

0.5 MBq
Tumor volume (mm3)

Recently, much attention has been directed towards
the powerful cancer therapeutic potential of targetedalpha-particle therapy (TAT). Globally, particularly inJapan, the α-particle emitting radionuclide astatine211 (211 At) has garnered signiﬁcant attention for its
use in TAT.
One of the crucial challenges in TAT is the delivery of 211 At to the tumor tissues. In a previous study,
we discovered that 211 At could be eﬃciently incorporated into gold nanoparticles (AuNPs) through a simple mixing process for 5 min, leading to a high radiochemical yield (RCY) without the need for puriﬁcation. Furthermore, our research revealed that the intratumoral administration of 211 At-AuNPs eﬀectively
suppresse tumor growth and demonstrate the stabilityof 211 At-AuNPs in the body.1) For systemic metastatictumors, intravenous injection is a promising method ofdelivery. In this study, we investigated the substantial
potential of AuNPs as carriers for the targeted deliveryof 211 At via intravenous administration.
211
At was produced at RIKEN using a short-lived
RI supply platform. The separation and puriﬁcationof 211 At was achieved through dry distillation. Fourtypes of functional AuNPs were synthesized throughsurface modiﬁcation using methoxy polyethylene glycol (mPEG) or tumor-targeting peptides (H16 orRGD). The astatine labeling reaction was evaluatedusing centrifugation, as described previously.1)
Tumor xenograft models were established thoroughthe subcutaneous transplantation of human pancreatic cancer cells (PANC-1) in BALB/c-nu/nu mouse.
Four types of 211 At-AuNPs were administered toPANC-1 xenograft mice to evaluate their biodistribution at 3 and 24 h. The treatment eﬀect of 5 nm
211
At-AuNPs@mPEG was evaluated using the PANC1 xenograft model. All the animal experiments wereconducted according to the guidelines of the Animal
Research: Reporting In Vivo Experiments and the Osaka University Animal Experiment Regulations, andapproved by the Osaka University Animal ExperimentCommittee.
Four types of 211 At-labeled functional AuNPs (5 nm211At-AuNPs@mPEG, 30 nm 211 At-AuNPs@mPEG,

100

32.5
21.5
10.5

10071421Days after injection

280CTL

0.5 MBq

1 MBq

Treatment

Fig. 1. (a) Four types of 211 At-labeled functional AuNPs
designed for the study.
(b) Change in the tumor size following the administration of 5 nm 211 AtAuNPs@mPEG or control (CTL) (saline). (c) Weightof enucleated tumors 30 d after injection.

The in vivo biodistribution results indicated a higheraccumulation of 5 nm 211 At-AuNPs@mPEG in tumors(2.25%ID/g) in 3 h when compared with 30 nm 211 AtAuNPs@mPEG based on the enhanced permeabilityand retention (EPR) eﬀect with a long retention timein tumors for 24 h. The intravenous administration of
5 nm 211 At-AuNPs@mPEG was found to signiﬁcantly
inhibit tumor growth in a pancreatic cancer model.
Gold nanoparticles (AuNPs) are an ideal carrier for211
At delivery, owing to their facile and eﬃcient synthesis processes and high stability. The results of thisstudy indicate that the intravenous administration of
5 nm 211 At-AuNPs@mPEG exhibits a potent antitumor eﬀect. These results provide a novel framework
for the design of nanoparticles suitable for targetedalpha-particle therapy via intravenous injection.2)
References
1) H. Kato et al., J. Nanobiotechnology 19, 1 (2021).
2) X. Huang et al., Pharmaceutics 14, 2705 (2022).