Ⅲ-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 53

Preparation of [211 At]-labeled sodium astatide (NaAt) by reducing withascorbic acid for the treatment of thyroid cancer†
Y. Shirakami,∗1 K. Kaneda,∗1 A. Toyoshima,∗1,∗2 T. Watabe,∗3 K. Ooe,∗1,∗3 A. Shinohara,∗4 and J. Hatazawa∗4Iodine-131 (131 I)-labeled sodium iodide, [131 I]-NaI, hasbeen used in clinics as the standard medication for patients with thyroid cancer. NaI can be transferred intocancer cells via sodium-iodide symporters (NIS), resulting in cell death owing to β − particles emitted from the131
I atoms. The agent has some limitations: i) [131 I]-NaI
does not work in some patients, even though the agent
accumulates in tumor lesions, and ii) the patients treatedwith the drug require isolated hospitalization within aweek.
[211 At]-NaAt is expected to be a novel therapeutic
agent for patients with thyroid cancer as an alternative
to [131 I]-NaI because the linear energy transfer (LET) of
211
At is much higher than that of 131 I. Several papers
have proven the eﬃcacy of the drug in animals and humans.1,2) The drug, however, has not been well evaluatedin humans yet. One of the major problems of the agent isthe diﬃculty in the chemical identiﬁcation of NaAt due
to the lack of a stable isotope of astatine. The aim ofour study is to develop methods for the quality controlof the drug.
Bismuth-209 was irradiated with helium-4 (α) at
29 MeV, and 211 At was produced through the209Bi(α, 2n)211 At reaction. The target was placed in aquartz tube and heated up to 850◦ C under a mixture ofhelium and oxygen gas ﬂow (30 mL/min and 10 mL/min,respectively). Dry-distillated 211 At was collected in ateﬂon tube cooled in an ice-water bath. Through thetube, 100 µL of distillated water was passed, and an
aqueous solution of 211 At (bulk solution) was collected
in a micro PFA vial.
An aqueous solution of [211 At]-NaAt was prepared using the following procedures. An aliquot of the bulk solution was transferred to a glass vial containing an aqueous
solution of 7 w/v% sodium hydrogen carbonate. Subse-Fig. 1. TLC profiles of the [211 At] bulk solution and [211 At]NaAt. Plate: Silica gel, Solvent: acetonitrile/water (2/1).
†∗1
∗2
∗3
∗4Condensed from the article in J. Nucl. Med. 60, 1301 (2019)
Institute for Radiation Sciences, Osaka University
RIKEN Nishina Center
Graduate School of Medicine, Tracer Kinetics and NuclearMedicine, Osaka University
Research Center for Nuclear Physics, Osaka University

Fig. 2. HPLC profiles of [211 At]-NaAt.
Column: reversed phase C-18 (Nakarai Tesque, Kyoto). Solvent:
20 mmoL/L tetrabutylammonium chloride/acetonitrile(7 : 3). Upper: UV trace, Bottom: RI trace.

quently, an aqueous solution of 3 w/v% ascorbic acid wasadded to the vial. The mixture solution was kept for 1 hat room temperature. The radioactivity of the solution
was adjusted to 10 MBq/mL.
Representative TLC proﬁles of the [211 At] bulk solution and [211 At]-NaAt are shown in Fig. 1. The [211 At]
bulk solution was comprised of several radioactive spots
having irregular shapes (Fig. 1, upper). This result indicated that the bulk solution is a mixture of several chemical species of 211 At, including the higher oxidation statesof astatine (At+ and/or At3+ ) as well as astatide ion(At− ). The radioactive species were converged on a single component (relative to front (Rf) = 0.9, radiochemical purity (RCP) > 90%) after the addition of ascorbic
acid (Fig. 1, bottom). The component was also presented
as the major radioactive peak (retention time (Rt) =7.42 min, RCP > 90%) by high-performance liquid chromatography (HPLC) analysis, as shown in Fig. 2. The
component was estimated to be [211 At]-NaAt.
In thyroid cancer cells, the solution of [211 At]-NaAt
was accumulated in cells speciﬁcally via NIS. The solution also inhibited tumor growth in mice with thyroidcancer.
These results suggest that ascorbic acid is eﬃcient forthe preparation of [211 At]-NaAt having high radiochemical purity. In conclusion, it is proved that [211 At]-NaAt
is a promising agent for the treatment of patients withthyroid cancer.
References

1) J. G. Hamilton et al., Exp. Biol. Med. 86, 366 (1954).
2) S. Carlin et al., J. Nucl. Med. 44, 1827 (2003).

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