III-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 54 (2021)

RIKEN Accel. Prog. Rep. 54 (2021)

Targeted alpha therapy for thyroid cancer: Radiation-induced toxicityof [211 At]NaAt in mice†
Y. Liu,∗2 T. Watabe,∗2,∗3 K. Kaneda-Nakashima,∗3,∗4 K. Ooe,∗1,∗2 Y. Shirakami,∗3 A. Toyoshima,∗1,∗3E. Shimosegawa,∗2 T. Nakano,∗3,∗5 A. Shinohara,∗3,∗4 and J. Hatazawa∗3,∗5
Radioactive iodine (RAI) therapy is used for the treatment of patients with diﬀerentiated thyroid cancer.1,2)
However, a percentage of patients shows insuﬃcient
131I accumulation3) or low therapeutic eﬀect even withenough 131 I accumulation, and some patients suﬀer fromrecurrence or metastases and become RAI-refractoryduring follow-up.4,5) For these patients, a more eﬀective
treatment is required.
Astatine (211 At) is a halogen with chemical properties similar to those of iodine, but it emits alpha particles, and we have found that the radiochemical purityof astatide dramatically improves upon treatment with
1% ascorbic acid. Consequently, the uptake of 211 At increases in the thyroid gland and thyroid cancer cells.7)
In this study, we evaluated the radiation-induced toxicity of diﬀerent doses of 211 At-NaAt solution at diﬀerent
time points to estimate its time-dependent toxicity.
Methods
The biodistribution of 211 At-NaAt was measured innormal ICR mice (n = 12) and the absorbed doses inmajor organs were calculated.
Groups of ICR mice (n = 60) were injected with
0.1 MBq or 1 MBq of 211 At-NaAt using saline as the control group (n = 30). Their body weight and food intakewere followed up for 60 days. The blood cell count andserum level of biochemical parameters were measured 3,7, 15, 29, and 60 days after injection. Histological analyses of major organs with hematoxylin and eosin staining
were performed.

Fig. 2. Evaluation of hematological toxicity in the control,
0.1 MBq, and 1 MBq groups.

Fig. 3. Histological changes in the thyroid gland (left) andtestis (right) evaluated by HE staining in the 1 MBq groupon day 29.

Results
Figure 1 revealed a high-absorbed dose in the thyroid
gland, stomach, bladder, heart, lungs, spleen, kidneys,and testes. The 0.1 MBq group showed no abnormalities.
The 1 MBq group showed decreased body weight andfood intake. Figure 2 showed that hematological toxicity
was mild and transient. The total cholesterol, albumin,
and total protein increased with no signs of recovery,
which can be attributed to hypothyroidism. Figure 3
showed atrophy and ﬁbrosis in the thyroid gland and atransient hypospermatogenesis was found in the testis of
one mouse on day 29.
Conclusion
High-dose administration of 211 At-NaAt showed transient toxicity in the white blood cells and testis without
severe hematological or renal toxicity, suggesting its tolerable safety as targeted alpha-therapy for diﬀerentiatedthyroid cancer in the 1 MBq group.

Fig. 1. %ID/g of main organs in normal ICR mice administered with 211 At-NaAt solution.
†∗1
∗2
∗3
∗4
∗5

Condensed from the article in Transl Oncol. 13, 4 100757(2020)RIKEN Nishina Center
Graduate School of Medicine, Osaka University
Institute for Radiation Sciences, Osaka University
Graduate School of Science, Osaka University
Research Center for Nuclear Physics, Osaka University

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5) M. Schlumberger et al., Lancet Diabetes Endocrinol. 2,356 (2014).
6) M. R. Zalutsky et al., Curr. Pharm. Des. 6, 1433 (2000).
7) T. Watabe et al., J. Nucl. Med. 60, 1301 (2019).

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