JPWO2020040296A1 - An anti-tumor agent containing a PEGylated boron cluster compound and a PEGylated boron cluster compound, and a sensitizer containing a PEGylated boron cluster - Google Patents

Abstract

As an enhancer of boron neutron capture therapy, a compound having an ideal effect and physical characteristics for the therapeutic principle is desired. As a solution thereof, the present invention comprises an antitumor containing a PEGylated boron cluster compound and a PEGylated boron cluster compound, characterized in that a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group are bonded. Agent, an enhancer containing a PEGylated boron cluster compound used in boron neutron capture therapy is provided.

Description

The present invention relates to a sensitizer used for radiotherapy of cancer and an active ingredient thereof.

One type of radiation therapy is boron neutron capture therapy (BNCT), which treats malignant tumors with alpha rays generated by the nuclear reaction between neutrons generated from reactors and accelerators and boron ( ^{10 B) taken into malignant tumors.} It has been known. Due to its principle, this therapeutic method can selectively destroy only tumor cells without damaging normal cells (Non-Patent Document 1).

Boronphenylalanine (BPA) and borocaptate (BSH), a monomolecular compound of boron ion clusters, are known as boron compounds used in BNCT clinical studies, but their therapeutic effects are sufficient from the viewpoint of tumor accumulation. However, it is necessary to further improve the boron concentration in the tumor and the boron concentration ratio (T / N ratio) in the tumor / normal tissue. Therefore, as a technique for accumulating boron at a high concentration only in tumor tissue, a method of encapsulating a hydrophilic boron compound such as BSH in a liposome whose surface is coated with polyethylene glycol (PEG) is used (Non-Patent Document). 2). However, even with these methods, it is difficult to accumulate boron up to an effective therapeutic range.

The following formula (II)

[In the equation, m and n are independently integers of 1 to 4, q is an integer of ^{1 to} 280, and R 1 and R ² are independent of 8 to 22 carbon atoms, respectively. It is a hydrocarbon group of. ]
Boron cluster-modified PEG lipid derivatives (PBL) having the above structure and liposomes coated on the membrane surface are also known (Patent Document 1), but development of a compound showing a stronger effect is desired.

Japanese Patent No. 6206925

Yamamoto Tea, Nakai Kay, Kagayi Tea, Kumada Eichi, Pea Kay, Mazda M, And Matsumura A, Radiotherapy and Oncology, April 2009, Vol. 91, No. 1, pp. 80-84 Matsuyama Kei, Ishida O, Casaoka S, Takizawa Tea, Utoguchi N, Shinohara A, Ciba M, Kobayashi H, Eriguchi M, Yanagi H, Journal of Control Release, 2004, August 11, 98, No. 2, 195 ―Page 207

The known boron compounds used in boron neutron capture therapy have been evaluated to a certain degree, but there are many cases of recurrence, and they are not ideal drugs. From the principle of boron neutron capture therapy, the conditions required for an ideal drug are that the boron concentration in the tumor is 20 ppm or more, the boron concentration ratio (T / B ratio) in the tumor / blood, and the boron concentration in the tumor / normal tissue. It is necessary that the ratio (T / N ratio) is 5 or more and that the compound is water-soluble, and a compound satisfying such conditions has been sought.

The present invention
[1] A PEGylated boron cluster compound, characterized in that a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group are bonded.
[2] The PEGylated boron cluster compound according to [1], wherein the boron cluster having a thiol group is a monomolecular compound borocaptate (BSH) of a boron ion cluster.
[3] The PEGylated boron cluster compound according to [1] or [2], wherein the multi-arm polyethylene glycol is a tetrafunctional group type.
[4] The structural formula is the following formula (1)

[In the equation, m, n, p, and q are integers 1 to 100 that are the same or different. ]
The PEGylated boron cluster compound according to any one of [1] to [3], which is represented by.
[5] The structural formula is as follows

The PEGylated boron cluster compound according to any one of [1] to [4], which is represented by.
[6] An antitumor agent comprising the PEGylated boron cluster compound according to any one of [1] to [5].
[7] An enhancer used for radiotherapy of a tumor, which comprises the PEGylated boron cluster compound according to any one of [1] to [5] as an active ingredient.
[8] The enhancer according to the radiotherapy according to [7] is neutron capture therapy, and the tumor according to [9] [7] or [8] is malignant brain tumor, malignant mesothelioma. For enhancers characterized by head and neck tumors, liver cancers, lung cancers, mesotheliomas, or bone and soft sarcoma.
The present invention also
[10] Boron neutron capture therapy for tumors, which comprises using the PEGylated boron cluster compound according to any one of [1] to [4].
[11] Boron neutron capture therapy for tumors according to [10], wherein the tumor is a malignant brain tumor, a malignant melanoma, a head and neck tumor, a liver cancer, a lung cancer, a mesenteric tumor, or a bone and soft sarcoma. Regarding.

FIG. 1 shows the results of a purity analysis LC chromatogram of BAMP. FIG. 2 shows the results of TOF-MS of BAMP. FIG. 3 shows the results showing the antitumor effect of BAMP and BSH. FIG. 4 shows the antitumor effects of BAMP and BSH, PBL-modified liposomes and BSH-encapsulated PBL-modified liposomes. FIG. 5 is a diagram showing the antitumor effect of BAMP and BPA. FIG. 6 is a diagram showing the antitumor effect of the BAMP 24 mg ¹⁰ B / Kg administration group and the BAMP ^{10 mg 10 B / Kg administration group.}

The PEGylated boron cluster compound of the present invention is characterized in that a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group are bonded.

In the present invention, the boron cluster is a monomolecular compound of a boron ion cluster, which is a carborane, dodecaborate, an ion cluster whose molecular formula is represented by _{B 10} H _{10 , and whose molecular formula is M (C 2} B ₉ H ₁₀ ) 2. It is selected from sandwich-type ion clusters represented by (M is a transition element) (these may have substituents). However, it is particularly preferable to use borocaptate (BSH) as the compound bonded to the thiol group.

The multi-arm polyethylene glycol imparted with a maleimide functional group is a multi-arm polyethylene glycol having a branched shape of 3-8, preferably 4 PEGs in polyethylene glycol (PEG), which is bonded to another compound. A compound in which a maleimide functional group for chemical modification is bonded to multi-arm polyethylene glycol. The number of maleimide functional groups bonded to the malmulti-arm polyethylene glycol may be two or more, preferably four. Such multi-arm polyethylene glycol is commercially available as a polyethylene glycol modifier for DDS, Sunbright (trade name, manufactured by Yuka Sangyo Co., Ltd.), and as a compound in which two maleimide functional groups are bonded to multi-arm polyethylene glycol, Sunbright 2TS-GL2-020BO3, Sunbright 2TS-GL2-020AZ3, Sunbright 2TS-B12-AZ, Sunbright 2TS-B12-DB, Sunbright 2TS-B12-BO, and three maleimide functional groups are maleimide functional groups. Examples of the compound bonded to the multi-arm polyethylene glycol include Sunbright 2TS-B12-BO and Sunbright 2TS-GL2-020MA4, and examples of the compound in which four maleimide functional groups are bonded to the malmultiarm polyethylene glycol include Sunbright. Examples thereof include PTE-100MA, Sunbright PTE-200MA, and Sunbright PTE-400MA, and particularly preferably, it is a compound in which four maleimide functional groups are bonded to multi-arm polyethylene glycol. Although the trade name was used as an example of the multi-arm polyethylene glycol imparted with a maleimide functional group, it is included in the multi-arm polyethylene glycol of the present invention as long as the structure is the same even if the trade names are different.

The PEGylated boron cluster compound according to the present invention, which comprises a bond between a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group, includes a compound of the following formula (I).

[In the equation, m, n, p, and q are integers 1 to 100 that are the same or different. ]
In the above formula (I), m, n, p, and q indicating the degree of polymerization of polyethylene glycol represent the same or different integers of 1 to 100, preferably 30 to 60, and more preferably 40 to 50. .. Particularly preferable structures of the present invention include the following compound BAMP (boron attached multi-arm peg).

The method for producing a PEGylated boron cluster compound of the present invention differs between a boron cluster having a thiol group and a multi-arm polyethylene glycol having a maleimide functional group, depending on the number of functional groups and the molecular weight of the multi-arm polyethylene glycol. 1 to 1 to 10, preferably 1 to 2, at room temperature of 10 to 30 ° C., preferably around 20 ° C., in a buffer solution of pH 7.0 to pH 9.0, preferably pH 8.0. The reaction is carried out for 5 hours, preferably 2.5 hours to 3.5 hours, with stirring. The buffer may be any buffer such as phosphate buffer and Tris-hydrochloric acid buffer, but it is particularly preferable to use phosphate buffered saline (PBS).

The obtained reaction solution is desalted by a dialysis method or the like to remove unnecessary small molecules, and then stored as a solid by a freeze-drying method. Specifically, the reaction solution was placed in a dialysis tube or the like, distilled water or the like was used as the external solution, and dialysis was performed for 36 to 72 hours, preferably 48 hours while exchanging the external solution as needed. A solidified boron PEGylated cluster compound can be obtained by freeze-drying for an hour to 36 hours, preferably 24 hours.

The antineoplastic agent according to the present invention, which contains a PEGylated boron cluster compound characterized by bonding a boron cluster having a thiol group and a multi-arm polyethylene glycol having a maleimide functional group, is the PEG. Indicates a drug that contains a boron PEGylation cluster compound and has a function of inhibiting the growth and division of tumor cells by α-rays emitted by boron absorbed in or near the tumor by a nuclear reaction with neutrons, and is an oral preparation or injection. Although it can be used as an agent, it is preferably used as an injection. Any tumor may be used for which the antitumor agent is used, and examples thereof include malignant brain tumor, malignant melanoma, head and neck tumor, liver cancer, lung cancer, mesothelioma, and bone and soft tissue sarcoma.

An enhancer used for radiotherapy of a tumor, which comprises a PEGylated boron cluster compound, which is characterized in that a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group are bonded in the present invention. In boron neutron capture therapy (BNCT), which is one of the radiotherapy, α that penetrates into tumor cells in advance and emits boron by neutron rays in order to enhance the growth inhibition or killing effect of tumor by neutrons. Any enhancer containing a PEGylated boron cluster compound, which has a growth-inhibiting or killing effect on tumor cells by the line and can be an enhancer of boron neutron capture therapy (BNCT), is usually used as an oral preparation or an injection of a drug. It preferably has the form of an injection.

The oral agent, topically absorbed preparation or injection agent in the antitumor agent and the enhancer used for radiotherapy is a PEG characterized by binding of a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group. The PEGylated boron cluster compound can be easily formulated by combining a pharmaceutically acceptable carrier known in the art.

The injection can be prepared in the form of an injection by a conventional method as a solution or a solid form suitable for dissolving in a liquid before injection. Suitable excipients are, for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine hydrochloride and the like. In addition, the injectable pharmaceutical composition may optionally contain small amounts of non-toxic auxiliary substances such as wetting agents, pH buffers and the like. Physiologically compatible buffers include, but are not limited to, Hanks' solution, Ringer's solution or saline buffer.

Topical gelling agents, creams, ointments, tablets, capsules, etc. used for oral administration can be prepared by a conventional method, and liquids such as solutions, suspensions, and emulsions; gels. , Paste-like, cream-like, or other semi-solid form; powdery, granular, tablet, or solid form such as capsules encapsulated in hard or soft capsules.

Additives used in the above formulations include excipients, binders, disintegrants, lubricants, coatings, bases, solvents, emulsifiers, dispersants, suspending agents, stabilizers, thickeners, pH. Examples include regulators, antioxidants, preservatives, preservatives, flavoring agents, sweeteners, flavors, colorants and the like.

Excipients include silicic anhydride, calcium silicate, magnesium silicate aluminate, starch (corn starch, potato starch, wheat starch, etc.), sugars (dextrose, lactose, sucrose, etc.), sugar alcohols (sorbitol, maltitol, etc.). , Mannitol, etc.) and the like.

Examples of the binder include gelatin, sodium caseinate, starch and processed starch (corn starch, hydroxypropyl starch, pregelatinized starch, partially pregelatinized starch, etc.), cellulose and its derivatives (crystalline cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, etc.), etc. Can be mentioned.

Examples of the disintegrant include povidone, crospovidone, cellulose and its derivatives (crystalline cellulose, methyl cellulose, etc.).

Examples of the lubricant include talc, synthetic aluminum silicate, magnesium silicate, calcium stearate, magnesium stearate and the like.

Examples of the coating agent include a methacrylic acid copolymer (methacrylic acid / ethyl acrylate copolymer, etc.), a methacrylate copolymer (ethyl acrylate / methyl methacrylate copolymer, ethyl acrylate / methyl methacrylate / chloride methacrylate, etc.). (Trimethylammonium ethyl copolymer, etc.) and the like.

Examples of the base include hydrocarbons (liquid paraffin and the like), polyethylene glycol (macrogol 400, macrogol 1500 and the like) and the like.

Examples of the solvent include purified water, monohydric alcohol (ethanol, etc.), polyhydric alcohol (propylene glycol, glycerin, etc.) and the like.

Examples of the emulsifier include nonionic surfactants (sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, etc.), anionic surfactants (sodium alkyl sulfate, N-acylglutamate, etc.). ), Purified soybean lecithin and the like.

Dispersants include gum arabic, propylene glycol alginate, nonionic surfactants (polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene glycol, etc.), anionic surfactants (polyoxyethylene polyoxypropylene glycol, etc.) Alkyl sulfate sodium, etc.) and the like.

Examples of the suspending agent include sodium alginate, nonionic surfactants (polyoxyethylene lauryl ether, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, propylene glycol fatty acid ester, etc.) and the like.

Examples of the stabilizer include adipic acid, ethylenediaminetetraacetic acid salt (calcium disodium salt, disodium salt, etc.), α-cyclodextrin, β-cyclodextrin and the like.

Examples of the thickener include water-soluble polymers (sodium polyacrylate, carboxyvinyl polymer, etc.), polysaccharides (sodium alginate, xanthan gum, tragant, etc.) and the like.

Examples of the pH adjuster include hydrochloric acid, phosphoric acid, acetic acid, citric acid, lactic acid, sodium hydroxide, sodium hydrogen phosphate and the like.

Ideally, the dose of the antitumor agent and the enhancer used for radiotherapy of the present invention is preferably 20 ppm or more in the tumor, and the dosage is a drug depending on the molecular weight of each active ingredient. Depending on the patient's body weight, 30 mg / Kg-300 mg / Kg, preferably 30 mg / Kg-200 mg / Kg, more preferably 30 mg / Kg-100 mg / Kg is administered. Since the neutron irradiation site in BNCT differs depending on the position of the tumor, it is necessary to apply the administration site to various sites such as intravenous, subcutaneous, and intramuscular. The dosing interval is also determined by the BNCT treatment policy, but it may be completed with a single dose.

An example of prescription is shown below.
Prescription example (injection)
BAMP lyophilized powder 1800mg
Distilled water for injection 100 ml
Phosphate buffer Appropriate amount 100 ml
Such compounds can be used as is, in the form of pharmaceutically acceptable salts, or mixed with them in the form of formulations known to those skilled in the art, such as BSH-encapsulated viral envelope vectors. In form, it can be conveniently used for boron neutron capture therapy (BNCT).

The BNCT treatment using the PEGylated boron cluster compound preparation of the present invention is carried out by administration by an arbitrary appropriate route of administration in such a manner that the PEGylated boron cluster compound accumulates in the target tumor. The PEGylated boron cluster compound is preferably concentrated in the tumor prior to irradiation, preferably with a tumor: blood ratio of about 2: 1 or at least 1.5: 1 before irradiation. The PEGylated boron cluster compound can be administered all at once or sequentially. After the compound has desirablely accumulated in the tumor, the site is irradiated with an effective amount of low-energy neutrons. The site can be irradiated through the skin, or the site can be completely or partially exposed prior to irradiation. Administration of the PEGylated boron cluster compound followed by irradiation can be repeated as needed. If desired, the tumor is surgically removed to the extent possible and then the remaining tumor is destroyed using the PEGylated boron cluster compound of the present invention. In another embodiment, the patient is administered an appropriate amount of PEGylated boron cluster compound and irradiated with an effective amount of ^{252 californium, a naturally occurring neutron radioactive material.} It is preferably inserted into the tumor and removed at an appropriate time.

Here, the type of tumor is not particularly limited, but brain tumors including glioblastoma and malignant glioma, malignant melanoma, breast cancer, prostate cancer and the like can be particularly suitable targets. In addition, epithelial cell cancers such as lung cancer, uterine cancer, kidney cancer, and liver cancer, and various sarcomas can also be targeted.

[Example 1]
120 mg of Sunbright PTE-100MA (manufactured by Yuka Sangyo Co., Ltd.), which is a multi-arm polyethylene glycol imparted with four maleimide functional groups, and 10B enriched sodium mercaptodecaborate (abbreviation), which is a monomolecular compound of boron ion clusters. 60 mg of BSH (manufactured by Katchem) was reacted in 10 ml of phosphate buffered saline (PBS) having a pH of 8.0 by mixing and stirring under room temperature conditions for 3 hours. The reaction was carried out while confirming the degree of progress by high performance liquid chromatography (HPLC).

The reaction mixture was placed in a dialysis tube (MWCO: 500 to 1000), placed in distilled water of the dialysis external solution, and dialyzed for 48 hours while exchanging the dialysis external solution every 12 hours. The reaction solution desalted by dialysis was freeze-dried for 24 hours to obtain a reaction product. Purity analysis LC chromatogram [column name: ACUITY UPLC BECH C18 (manufactured by Waters), eluent A: 0.1% TEA / H ₂ O, eluent B: 0.2% TFA / ACN, gradient conditions: B25%, 6 minutes, 99% 0.5 mL / min, column temperature 50 ° C., analysis time 6.8 minutes] and TOF-MS [Shimadzu Biotech AXIMA (trade name:) Shimadzu)]. The results are shown in FIGS. 1 and 2. The purity of the obtained BAMP was 99.8%.
[Example 2]
BAMP, BSH (manufactured by Katchem) obtained in Example 1, PBL-BSH (BSH encapsulated in liposomes) and PBL modification obtained by encapsulating BSH in PBL-modified liposomes by a conventional method. Four kinds of test compounds of liposomes (PBL-plane) were administered to cancer-bearing mice, and the therapeutic enhancement effect and antitumor effect at the time of performing boron neutron capture therapy (BNCT) were examined.
The cancer-bearing mouse model was a BALB / cA mouse (female, 5 weeks old, body weight 16-20 g) inoculated with mouse colon cancer cells (CT26.3 x 10 ⁶ cells) in the right thigh, and had a tumor diameter of 6-8 mm. It was made to be.
Approximately 14 days after the treatment, the test compound was intravenously injected into the tail at a concentration ^{of 10 mg 10 B / Kg in terms of boron (57 mg 10} B / Kg concentration so that the most antitumor effect was obtained in the BSH-administered group). In addition, the pre-administration was not performed in the radiation-only group (control) and the untreated group.
After 24 hours, neutron irradiation was performed in the Kyoto University Research Reactor (KUR). The neutron dose was 5.2 x 10 ¹² neutron / cm ² , and the irradiation time was 2 hours. The tumor suppressive effect was measured by measuring the tumor diameter after irradiation by the 26th day over time, and compared with the control group. For control, a comparative study was conducted using a group that received only neutron irradiation and a group that did not receive or administer neutrons (untreated group). The tumor size was measured by the following formula.
[Major axis (mm)] X [minor (mm)] ^2/2 = tumor size ^(mm 3)
As a result, when comparing the tumor sizes of the BAMP-administered group and the BSH-administered group, the antitumor effect of the BAMP-administered group was significantly stronger than that of the BSH-administered group, even though the BSH-administered group had a higher boron dose. (Fig. 3).

In addition, the BAMP-administered group had a significantly stronger antitumor effect than the PBL-BSH group in which BSH was encapsulated in PBL-modified liposomes (Fig. 4).
[Example 3]
Two types of test compounds, BAMP and BPA (manufactured by Interpharma) obtained in Example 1, were administered to cancer-bearing mice to obtain a therapeutic enhancing effect and an antitumor effect during boron neutron capture therapy (BNCT). investigated. The cancer-bearing mouse model was a BALB / cA mouse (female, 4 weeks old, body weight 16-20 g) inoculated with mouse colon cancer cells (CT26.5 x 10 ⁶ cells) in the right thigh, and had a tumor diameter of 6-8 mm. It was made to be.
Approximately 12 days after the treatment, BAMP was intravenously injected into the tail at a dose ^{of 10 mg 10} B / Kg and 24 mg ¹⁰ B / Kg as a boron equivalent, and BPA was administered intravenously at a dose of 10 mg ^{10 B / Kg as a boron equivalent.} ..
The BAMP-administered group was irradiated with neutrons 36 hours later, and the BPA-administered group was irradiated with neutrons 2 hours later in the Kyoto University Research Reactor (KUR). The neutron dose was 1.8-4.0 x 10 ¹² neutron / cm ² for 1 hour. The antitumor effect was measured by measuring the tumor diameter after irradiation by the 24th day over time, and compared with the control group in which only irradiation was performed. We also conducted a comparative study using the untreated group, which was neither administered nor irradiated. The tumor size was measured by the following formula.
[Major axis (mm)] X [minor (mm)] ^2/2 = tumor size ^(mm 3)
As a result, when comparing the tumor size of BAMP administration group and BPA administration group, BAMP10mg ¹⁰ B / Kg dose group than BPA10mg ¹⁰ B / Kg dose group, the anti-tumor effect was significantly higher (Figure 5) ..
In addition, the BAMP 24 mg ¹⁰ B / Kg administration group had a ^{significantly higher antitumor effect than the BAMP 10} mg 10 B / Kg administration group (Fig. 6), and the effect of BAMP was dose-dependent.

INDUSTRIAL APPLICABILITY The present invention provides an antitumor agent / radiological sensitizer having high water solubility ideal for boron neutron capture therapy, a boron concentration of 20 ppm or more in a tumor, and a T / B ratio of 5 or more. NS.

BAMP: BAMP administration group BSH: BSH administration group PBL-BSH: BSH administration group encapsulated in PBL-modified liposome PBL-plane: PBL-modified liposome administration group irradiation only2hour: neutron beam 2 hours irradiation group irradiation only1hour: neutron beam 1 hour Irradiation group no treatment: untreated group BAMP ¹⁰ mgB / Kg: BAMP 10 mg 10 B / Kg administration group BAMP 24 mg B / Kg: BAMP 24 mg ¹⁰ B / Kg administration group BPA ¹⁰ mg B / Kg: BPA 10 mg 10 B / Kg administration group irradiation only: neutron irradiation time

Claims (11)

A PEGylated boron cluster compound characterized in that a boron cluster having a thiol group and a multi-arm polyethylene glycol imparted with a maleimide functional group are bonded. The PEGylated boron cluster compound according to claim 1, wherein the boron cluster having a thiol group is a monomolecular compound borocaptate (BSH) of a boron ion cluster. The PEGylated boron cluster compound according to claim 1 or 2, wherein the multi-arm polyethylene glycol is a tetrafunctional group type. The structural formula is the following formula (1)

[In the equation, m, n, p, and q are integers 1 to 100 that are the same or different. ]
The PEGylated boron cluster compound according to any one of claims 1 to 3, wherein the PEGylated boron cluster compound is represented by. The structural formula is as follows

The PEGylated boron cluster compound according to any one of claims 1 to 4, wherein the PEGylated boron cluster compound is represented by. An antitumor agent containing the PEGylated boron cluster compound according to any one of claims 1 to 5. An enhancer used for radiotherapy of a tumor, which comprises the PEGylated boron cluster compound according to any one of claims 1 to 5 as an active ingredient. The enhancer according to claim 7, wherein the radiotherapy is a neutron capture therapy. The enhancer according to claim 7 or 8, wherein the tumor is malignant brain tumor, malignant melanoma, head and neck tumor, liver cancer, lung cancer, mesothelioma, or bone and soft sarcoma. A boron neutron capture therapy for a tumor, which comprises using the PEGylated boron cluster compound according to any one of claims 1 to 4. Boron neutron capture therapy of a tumor according to claim 10, wherein the tumor is a malignant brain tumor, a malignant melanoma, a head and neck tumor, a liver cancer, a lung cancer, a mesenteric tumor, or a bone and soft sarcoma.

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