Nuclear medicine therapeutic agent for thyroid cancer

Abstract

The purpose of the present invention is to provide a therapeutic agent for thyroid cancer with which 211At- (astatide ion) can be safely administered to a patient (human) and efficacy can be expected. The present invention provides a sodium astatide injection solution for treating thyroid cancer, the sodium astatide injection solution containing 211At- (astatide ion) and being intravenously administered as a single dose to a subject in need of treatment for thyroid cancer at a dose of 2-4 MBq / kg body weight or a dose of 100-400 MBq.

Description

Radionuclide therapeutic agent for thyroid cancer

[0001] The present invention relates to radioactive astatine ( ２１１ At)-containing therapeutic agent (injection) for thyroid cancer, which uses At as an active ingredient.

[0002] Currently, in the treatment of thyroid cancer, internal therapy using radioactive iodine ( １３１ I-NaI) (oral administration of sodium iodide capsules) is performed. The thyroid gland and thyroid cancer take up iodide ions ( １３１ I － ) via the sodium-iodide symporter. Therefore, when radioactive iodine is administered, the iodide ion １３１ I － accumulates in thyroid cancer lesions throughout the body, and the β-rays it emits can irradiate and treat the affected area from inside the body. In addition to being performed as ablation of the residual thyroid bed after total thyroidectomy, this treatment method is also used for the treatment of multiple metastasis cases. However, many patients do not obtain sufficient therapeutic effects with this treatment method using radioactive iodine. In particular, some patients cannot obtain a shrinking effect on metastatic lesions despite radioactive iodine being taken up by the lesions. One of the factors considered for these problems is that the cell-killing ability of β-rays emitted by iodide ion １３１ I － is insufficient. In addition, in the treatment of patients with multiple metastases using radioactive iodine, there is a risk of radiation exposure to the surroundings, so isolated hospitalization in a dedicated radiotherapy room is required. Hospitalization in such rooms imposes a great psychological burden on patients, and it is also difficult for many medical institutions to maintain radiotherapy rooms in terms of cost. For this reason, the number of therapeutic beds has been decreasing, and the waiting period for patients before treatment has been lengthening.

[0003] Astatine is taken up into cells via the sodium-iodide symporter in the same manner as iodine. Radioactive astatine ( ２１１Unlike radioactive iodine, which emits beta rays, astatine (At) emits alpha rays. Alpha rays have advantages over beta rays, such as a higher biological efficacy ratio. Because alpha rays can deliver a large amount of energy with a short range of only a few cells, it is expected that energy can be selectively concentrated in cancer cells while minimizing the impact on surrounding tissues, thereby achieving a great therapeutic effect. ２１１ Because radioactive astatine (At) emits very little gamma radiation, there is virtually no exposure to the surrounding area. Due to these characteristics, treatment using radioactive astatine does not require isolation in a dedicated radiation therapy room, allowing for early initiation of treatment on an outpatient basis. This reduces the psychological burden on patients and is also expected to lead to significant improvements in healthcare economics.

[0004] The present inventors, together with other inventors, ２１１ At － A method for producing a solution containing astatinide ions with high radiochemical purity (sodium astatinide injection solution) has been discovered, and studies using thyroid cancer cell (K1-NIS) transplanted mice have confirmed that the solution exhibits tumor-specific high accumulation (Patent Document 1). However, the dosage and administration method that can be safely administered to patients (humans) and is expected to be effective have not been investigated.

[0005] WO2019 / 131998

[0006] The objective of the present invention is, ２１１ At － The objective is to provide a thyroid cancer treatment drug that can be safely administered to patients (humans) using astatinide ions and is expected to be effective.

[0007] The inventors of this invention have conducted thorough research and found that ２１１ At － We completed the present invention by discovering that a sodium astatinate injection solution containing (astatinate ions) as an active ingredient can be safely administered once daily by intravenous administration at a specific dosage range described below, and that efficacy can be expected.

[0008] In other words, the present invention provides the following: [1] ２１１At － A sodium astatinide injection for the treatment of thyroid cancer, containing astatinide ions, to be administered intravenously at a dose of 2-4 MBq / kg body weight, at least as a single dose, to patients requiring treatment for thyroid cancer. [1'] ２１１ At － [1] A sodium astatinate injection for the treatment of thyroid cancer, containing (astatinate ions), to be administered intravenously as a single dose at a dose of 2 to 4 MBq / kg body weight to patients requiring treatment for thyroid cancer. [2] The injection according to [1] or [1'] above, wherein the dose is 2.5 to 3.5 MBq / kg body weight. [3] ２１１ At － A sodium astatinate injection for the treatment of thyroid cancer, containing astatinate ions, to be administered intravenously at a dose of 100-400 MBq to patients requiring treatment for thyroid cancer, at least as a single dose. [3'] ２１１ At － A sodium astatinide injection solution for the treatment of thyroid cancer, containing (astatinide ions), to be administered intravenously as a single dose at a dose of 100 to 400 MBq to patients requiring treatment for thyroid cancer. [4] The injection solution according to any one of [1], [1'], [2], [3], or [3'] above, wherein the target patient is a patient with refractory thyroid cancer. [5] ２１１ At － An injectable solution according to any one of the above [1], [1'], [2], [3], [3'], or [4], containing (astatinide ions) with a radiochemical purity of 90% or more. [6] ２１１ At － A method for treating thyroid cancer, comprising administering a sodium astatinide injection solution containing (astatinide ions) to a patient requiring treatment for thyroid cancer at a dose of 2-4 MBq / kg body weight, at least as a single intravenous dose. [6'] ２１１ At －A method for treating thyroid cancer, comprising administering a sodium astatinide injection solution containing (astatinide ions) as a single intravenous dose at a dose of 2 to 4 MBq / kg body weight to a subject requiring treatment for thyroid cancer. [7] The method according to [6] or [6'] above, wherein the dose is 2.5 to 3.5 MBq / kg body weight. [8] ２１１ At － A method for treating thyroid cancer, comprising administering a sodium astatinide injection solution containing (astatinide ions) to a patient requiring treatment for thyroid cancer at a dose of 100 to 400 MBq, at least as a single intravenous dose. [8'] ２１１ At － A method for treating thyroid cancer, comprising administering a sodium astatinate injection solution containing (astatinate ions) as a single intravenous dose of 100 to 400 MBq to a subject requiring treatment for thyroid cancer. [9] The method according to any one of [6], [6'], [7], [8], or [8'] above, wherein the subject of administration is a patient with refractory thyroid cancer.

[10] The sodium astatinate injection solution is ２１１ At － The method according to any one of the above [6], [6'], [7], [8], [8'], or [9], which contains (astatinide ions) with a radiochemical purity of 90% or more.

[11] For use in the treatment of thyroid cancer, ２１１ At － A sodium astatinate injection containing (astatinide ions), which is administered intravenously at a dose of 2-4 MBq / kg body weight, at least as a single dose, to subjects requiring treatment for thyroid cancer. [11'] For use in the treatment of thyroid cancer, ２１１ At － A sodium astatinate injection solution containing (astatinate ions), which is administered intravenously as a single dose at a dose of 2 to 4 MBq / kg body weight to a subject requiring treatment for thyroid cancer.

[12] The injection solution according to

[11] or [11'] above, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

[13] For use in the treatment of thyroid cancer,２１１ At － A sodium astatinate injection containing (astatinate ions), which is administered intravenously at a dose of 100 to 400 MBq, at least as a single dose, to a patient requiring treatment for thyroid cancer. [13'] For use in the treatment of thyroid cancer, ２１１ At － A sodium astatinate injection solution containing (astatinate ions), which is administered intravenously as a single dose at a dose of 100 to 400 MBq to a patient requiring treatment for thyroid cancer.

[14] The injection solution according to any one of

[11] , [11'],

[12] ,

[13] , or [13'] above, wherein the target patient is a patient with refractory thyroid cancer.

[15] ２１１ At － An injectable solution according to any one of the above

[11] , [11'],

[12] ,

[13] , [13'], or

[14] , containing (astatinide ions) with a radiochemical purity of 90% or more.

[16] For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１ At － Use of (astatinide ions), wherein the injection solution is administered intravenously at a dose of 2-4 MBq / kg body weight, at least as a single dose, to subjects requiring treatment for thyroid cancer. [16'] For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１ At － Use of (astatinide ion), wherein the injection is administered intravenously as a single dose at a dose of 2 to 4 MBq / kg body weight to a subject requiring treatment for thyroid cancer.

[17] Use according to

[16] or [16'] above, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

[18] For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１At － Use of (astatinide ions), wherein the injection solution is administered intravenously at a dose of 100 to 400 MBq, at least as a single dose, to subjects requiring treatment for thyroid cancer. [18'] For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１ At － Use of (astatinide ion), wherein the injection solution is administered intravenously as a single dose at a dose of 100 to 400 MBq to a subject requiring treatment for thyroid cancer.

[19] Use according to any one of

[16] , [16'],

[17] ,

[18] , or [18'] above, wherein the subject of administration is a patient with refractory thyroid cancer.

[20] The sodium astatinide injection solution is ２１１ At － The use described in any one of the above

[16] , [16'],

[17] ,

[18] , [18'], or

[19] , which contains (astatinide ions) with a radiochemical purity of 90% or more.

[0009] The injectable solution of the present invention can be safely administered to patients (humans) and is expected to be effective in the treatment of thyroid cancer. Furthermore, the injectable solution of the present invention eliminates the need for isolation and hospitalization in a dedicated radiation therapy room, which is required in conventional treatment of thyroid cancer using radioactive iodine. This allows for early initiation of treatment on an outpatient basis, reducing the mental burden on patients and is also expected to bring about significant improvements in terms of healthcare economics. The present invention provides a thyroid cancer treatment drug (injectable solution) that can be safely administered and is expected to be effective.

[0010] Figures 1 and 2 show one case in the 3.5 MBq / kg dose group in Test Example 1 (a case in which the treatment effect was partial remission (PR) close to complete remission (CR)). １３１ I] NaI scan test results ([ １３１ I) NaI-SPECT / CT images are shown. Figure 1 shows radioactive iodine after thyrogen loading. １３１Figure 1 shows a whole-body distribution image taken with a SPECT / CT scanner two days after oral administration of an I-NaI capsule (74 MBq), illustrating the distribution of metastatic lesions of thyroid cancer accompanied by iodine accumulation. The arrows in Figure 1 point to bone metastatic lesions in the lumbar spine and pelvis. Figure 2 is a SPECT / CT fused image taken after the planar imaging in Figure 1, followed by SPECT and CT imaging. The arrows in Figure 2 point to metastatic lesions of thyroid cancer accompanied by iodine accumulation.

[0011] The present invention will be described in detail below. The injectable solution of the present invention contains as an active ingredient ２１１ At － This is an aqueous solution (injectable solution) containing (astatinide ions). In the sodium astatinide injection solution of the present invention, sodium astatinide is present in the injection solution. ２１１ At － (Astatinide ion) and Na ＋ It exists in the form of (sodium ions).

[0012] The injectable solution of the present invention is administered to the target subject as a single intravenous dose at a dose of 2 to 4 MBq / kg body weight (preferably 2.5 to 3.5 MBq / kg body weight, more preferably 2.75 to 3.5 MBq / kg body weight, even more preferably 3 to 3.5 MBq / kg body weight, even more preferably 3.25 to 3.5 MBq / kg body weight, and particularly preferably 3.5 MBq / kg body weight). Repeated administration may also be performed as needed. Alternatively, the injectable solution of the present invention is administered to the target subject as a single intravenous dose at a dose of 100 to 400 MBq (preferably 138 to 308 MBq, more preferably 150 to 308 MBq, and even more preferably 163 to 308 MBq). Repeated administration may also be performed as needed. In the present invention, intravenous administration is preferably performed slowly, regardless of the dose per administration. For example, it is preferable to administer the drug slowly over approximately 30 seconds to approximately 2 minutes, and it is even more preferable to administer it slowly over approximately 1 minute.

[0013] In the present invention, in order to enhance the accumulation of astatine in the lesion, it is preferable to perform the following measures on the subject as a pre-treatment measure before administering the injection solution of the present invention: (1) Iodine restriction Iodine restriction is performed for a certain period before and / or after administering the injection solution of the present invention (for example, from two weeks before administration of the injection solution of the present invention to two days after administration). (2) Thyroid-stimulating hormone administration Thyroid-stimulating hormone (for example, thyrotropin alfa (preferably recombinant human thyrotropin alfa (trade name "Tyrogen (registered trademark) for intramuscular injection 0.9 mg", generic name: human thyrotropin alfa (recombinant), Sanofi K.K.))) is administered before administering the injection solution of the present invention). The method of administering human thyrotropin alfa (recombinant) is to administer 0.9 mg intramuscularly in the gluteal muscle for a total of two doses, 48 ​​hours and 24 hours before administration.

[0014] The injectable solution of the present invention is administered to individuals requiring treatment for thyroid cancer.

[0015] The injectable solution of the present invention is useful in that it can also be used in patients with refractory thyroid cancer. In this specification, patients with refractory thyroid cancer are those who have been exposed to radioactive iodine ( １３１ I) This refers to patients with thyroid cancer who do not achieve sufficient therapeutic effects with standard treatments such as those listed above. Specifically, refractory thyroid cancer patients include, for example, patients with thyroid cancer (papillary carcinoma, follicular carcinoma) after total thyroidectomy who have undergone three or more treatments. １３１ The treatment effect is insufficient in the course of I-NaI treatment. １３１ This refers to patients who are resistant to I-NaI treatment.

[0016] The present invention uses the following injectable solution: ２１１ At － An aqueous solution containing (astatinide ions) can be produced, for example, by the method described in WO2019 / 131998 or a similar method.

[0017] The present invention uses the following injectable solution: ２１１ At － Examples of methods for producing an aqueous solution containing (astatinide ions) include the following (1) and (2). (1) ２１１ At solution (２１１ To a stock At solution, add a reducing agent (e.g., ascorbic acid), a pH adjuster (e.g., sodium hydrogen carbonate), and water for injection as necessary, mix, ２１１ At － an astatide ion-containing aqueous solution with high radiochemical purity is obtained. (2) ２１１ At solution ( ２１１ stock At solution), add a reducing agent (e.g., sodium ascorbate) and water for injection as necessary, mix, ２１１ At － an astatide ion-containing aqueous solution with high radiochemical purity is obtained.

[0018] The injection solution of the present invention (an aqueous solution containing ２１１ At － astatide ions) may contain the reducing agent and the like added in the above production process. The injection solution may further contain additives generally used in pharmaceutical preparations, for example, solvents such as water for injection, physiological saline and alcohol, pH adjusters, buffer solutions, isotonic agents, surfactants, sweeteners, flavoring agents, coloring agents, stabilizers and excipients. These additives are used in conventional amounts in pharmaceutical preparations.

[0019] The pH of the injection solution of the present invention is preferably in the range of pH 6 to pH 9.

[0020] One embodiment of the injection solution of the present invention includes the alpha-ray nuclear medicine therapeutic agent TAH-1005 ( ２１１ At]NaAt).

[0021] The radiochemical purity of the injection solution of the present invention is preferably 30% or more, 50% or more, more preferably 80% or more, still more preferably 90% or more, even more preferably 95% or more, and particularly preferably 100%. As used herein, radiochemical purity refers to the percentage of the radioactivity of ２１１ astatide ions relative to the total radioactivity of At ２１１ At － in the aqueous solution (injection solution). The radiochemical purity in the present invention can be confirmed, for example, by the thin-layer chromatography method described in Test Example 1 of WO2019 / 131998, or a method equivalent thereto.

[0022] In the treatment method using the injection solution of the present invention, after administration to a patient, the drug accumulates in the affected area ２１１ and the affected area can be treated by irradiation with α-rays emitted by At. In the present invention, treatment of thyroid cancer includes those performed for the purpose of reducing, suppressing progression, or completely eliminating primary lesions, recurrent lesions, and metastatic lesions (e.g., bone metastatic lesions) of thyroid cancer.

[0023] Hereinafter, the present invention will be described in more detail based on test examples, but the present invention is not limited thereto.

[0024] [Test Example 1] Astatine-loaded sodium injection solution ([ ２１１ At]NaAt) Evaluation of Safety and Efficacy (Preparation of Test Drug (Astatine-loaded sodium injection solution ([ ２１１ At]NaAt))) By cyclotron ２０９ Bi(α,2n) ２１１ At produced by the nuclear reaction of ２１１ At was separated and purified by dry distillation and captured in a cooled trap tube. A 1% ascorbic acid-2.3% sodium bicarbonate mixed aqueous solution was passed through this tube to ２１１ dissolve At, and the solution was recovered in a reaction vial. The solution was further stirred at room temperature for 30 minutes or more to prepare astatine-loaded sodium injection solution ([ ２１１ At]NaAt). Regarding the recovery of ２１１ At from the trap tube to the reaction vial, the recovery rate was 94±6% (N=11), the production yield was 53±4% (N=11), and the radiochemical purity was 99±1% (N=11). (Test Methods and Results) The following tests were conducted on 11 patients with thyroid cancer (papillary cancer, follicular cancer) for whom standard treatment did not produce therapeutic effects, or for whom implementation or continuation of standard treatment is difficult. As pretreatment to increase the accumulation of astatine in lesions for the subjects, (1) iodine restriction was implemented from 2 weeks before administration of the test drug to 2 days after administration, and (2) one vial each of "Thyrogen (registered trademark) for intramuscular injection 0.9 mg" (trade name) was administered 24 hours and 48 hours before administration of the test drug. To the subject, the test drug (astatine-loaded sodium injection solution ([ ２１１A single intravenous dose of [At]NaAt) was administered (2 subjects at 1.25 MBq / kg, 3 subjects at 2.5 MBq / kg, and 6 subjects at 3.5 MBq / kg), and the presence or absence of dose-limiting toxicity (DLT) as shown below was observed within 4 weeks after administration. As a result, no dose-limiting toxicity was observed in any of the subjects (5 subjects) at more than 4 weeks after administration of the study drug, specifically in the 1.25 MBq / kg and 2.5 MBq / kg doses. Of the subjects at 3.5 MBq / kg, no dose-limiting toxicity was observed in 3 subjects, but dose-limiting toxicity due to hematological toxicity was observed in the remaining 3 subjects. The results (number of subjects with dose-limiting toxicity / number of subjects who underwent testing) are shown in Table 1.

[0025] [Dose-limiting toxicity (DLT)] Dose-limiting toxicity is defined as toxicity occurring within four weeks after administration of the study drug, where one or more of the following conditions cannot be ruled out as being causally related to the study drug: (1) Grade 3 toxicity lasting for 7 days or more ＊ (2) Hematological toxicity (grade 4, regardless of duration) ＊ The above hematological toxicities include: (3) Febrile neutropenia regardless of duration; (4) Thrombocytopenia accompanied by bleeding tendencies or requiring platelet transfusion; (5) Anemia requiring red blood cell transfusion; (6) Neutropenia associated with infection; (7) Grade 3 neutropenia lasting more than 7 days and not improving with symptomatic treatment. ＊ The above are non-hematological toxicities, except for the following: • Clinically insignificant abnormal clinical laboratory values ​​• Grade 2 with maximum supportive care ＊ The following are due to controllable toxicity or exacerbation of the underlying disease: ＊ (Grade as defined in CTCAE (Common Terminology Criteria for Adverse Events) v.5.0 JCOG version)

[0026] In the following tests (1) to (3): ２１１ The therapeutic effect of At[NaAt] was evaluated.

[0027] (1) Thyroglobulin levels (Tg decrease > 50%) The decrease in serum thyroglobulin levels after thyrogen loading was calculated at 3 months and 6 months after administration of the investigational drug compared to the time at screening. The results (number of cases with a Tg value decrease of 50% or more / number of cases in which the test was performed) are shown in Table 1. Cases with a Tg value decrease of 50% or more were observed in the 2.5 MBq / kg group and the 3.5 MBq / kg group.

[0028] (2) CT scan (6 months) Six months after administration of the investigational drug, plain CT scans (without contrast agent) were performed on the neck, chest, abdomen, and pelvic region, and the treatment effect was evaluated according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. The results (number of cases with CR, PR, SD, or PD / number of cases examined) are shown in Table 1. No tumor reduction effect (CR, PR) was observed in any of the treatment groups. (Although SD could be considered to be included in the treatment effect, here we considered tumor reduction of PR or better to be a treatment effect.)

[0029] (3) [ １３１ I] NaI scan test (6 months) [ １３１ I] Iodine restriction was performed from one week before NaI administration until two days after administration, followed by thyrogen loading. １３１ I) NaI 74 MBq was administered, and whole-body planar radiography and localized SPECT / CT radiography were performed using a SPECT / CT scanner. The treatment effect was evaluated according to the following criteria: a) CR (Complete response): If no significant abnormal uptake suggestive of metastasis or recurrence is observed, it is judged as CR. b) PR (Partial response): Compared to the initial screening, the abnormal uptake is visually significantly reduced, and it is judged as PR. c) PD (Progressive disease): Compared to the initial screening, the abnormal uptake is visually markedly worsened, or new lesions are observed, and it is judged as PD. d) SD (Stable disease): If the patient does not fall under CR, PR, or PD, and no significant change in uptake is visually observed, it is judged as SD.

[0030] The results (number of cases with CR, PR, SD, or PD / number of cases that underwent testing) are shown in Table 1. In addition, one case in the 3.5 MBq / kg dose group (a case in which the treatment effect was partial remission (PR) close to complete remission (CR)) is shown. １３１ I] NaI scan test results ([ １３１ I) NaI-SPECT / CT images are shown in Figures 1 and 2. Therapeutic effects on CR and PR were observed in the 2.5 MBq / kg group and the 3.5 MBq / kg group.

[0031] Based on the above results, at doses of 2.5 MBq / kg and 3.5 MBq / kg, [ ２１１ At]NaAt was found to have a therapeutic effect. In particular, at a dose of 3.5 MBq / kg, １３１ I) It was superior in that it was possible to confirm cases of complete remission (CR) in NaI-SPECT / CT images.

[0032]

[0033] According to the present invention, it is possible to provide a therapeutic agent for thyroid cancer that can be administered safely and is expected to be effective.

[0034] This application is based on Japanese Patent Application No. 2025-057100, the contents of which are entirely incorporated herein.

Claims

1. ２１１ At － A sodium astatinate injection solution for the treatment of thyroid cancer, containing astatinate ions, administered as a single intravenous dose of 2-4 MBq / kg body weight to patients requiring treatment for thyroid cancer.

2. The injectable solution according to claim 1, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

3. ２１１ At － A sodium astatinate injection solution for the treatment of thyroid cancer, containing astatinate ions, administered as a single intravenous dose of 100-400 MBq to patients requiring treatment for thyroid cancer.

4. The injectable solution according to any one of claims 1 to 3, wherein the target recipient is a patient with refractory thyroid cancer.

5. ２１１ At － An injectable solution according to any one of claims 1 to 3, containing (astatinide ions) with a radiochemical purity of 90% or more.

6. ２１１ At － A method for treating thyroid cancer, comprising administering a single intravenous dose of sodium astatinide injection solution containing astatinide ions to a patient requiring treatment for thyroid cancer at a dose of 2 to 4 MBq / kg body weight.

7. The method according to claim 6, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

8. ２１１ At － A method for treating thyroid cancer, comprising single intravenous administration of astatine-211 sodium injection containing (astatinate ion) at a dose of 100 to 400 MBq to a subject in need of thyroid cancer treatment.

9. The method according to any one of claims 6 to 8, wherein the target of administration is a patient with refractory thyroid cancer.

10. The sodium astatinate injection solution is ２１１ At － The method according to any one of claims 6 to 8, comprising (astatinide ions) with a radiochemical purity of 90% or more.

11. For use in the treatment of thyroid cancer, ２１１ At － A sodium astatinate injection solution containing (astatinate ions), which is administered intravenously as a single dose at a dose of 2 to 4 MBq / kg body weight to patients requiring treatment for thyroid cancer.

12. The injectable solution according to claim 11, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

13. For use in the treatment of thyroid cancer, ２１１ At － A sodium astatinate injection solution containing (astatinate ions), which is administered intravenously as a single dose of 100 to 400 MBq to patients requiring treatment for thyroid cancer.

14. The injectable solution according to any one of claims 11 to 13, wherein the target recipient is a patient with refractory thyroid cancer.

15. ２１１ At － An injectable solution according to any one of claims 11 to 13, containing (astatinide ions) with a radiochemical purity of 90% or more.

16. For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１ At － Use of (astatinide ions), wherein the injection solution is administered intravenously as a single dose at a dose of 2-4 MBq / kg body weight to subjects requiring treatment for thyroid cancer.

17. The use according to claim 16, wherein the dose is 2.5 to 3.5 MBq / kg body weight.

18. For the treatment of thyroid cancer ２１１ At － For the manufacture of sodium astatinide injection solution containing (astatinide ions), ２１１ At － Use of (astatinide ions), wherein the injection solution is administered intravenously as a single dose at a dose of 100 to 400 MBq to subjects requiring treatment for thyroid cancer.

19. The use according to any one of claims 16 to 18, wherein the target recipient is a patient with refractory thyroid cancer.

20. The sodium astatinate injection solution is ２１１ At － The use according to any one of claims 16 to 18, wherein the (astatinide ion) is contained with a radiochemical purity of 90% or more.

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