JP2019001761A - Tumor imaging agent, and oncotherapeutic agent for boron-neutron capture therapy - Google Patents

Abstract

To provide a tumor imaging agent exhibiting a sufficiently high accumulation ratio between tumor cells and normal cells.SOLUTION: The tumor imaging agent comprises a radioactive labeling compound represented by general formula (1) or a salt thereof. In the general formula (1), Rrepresents -F, -CH, -CFH, or -CFF.SELECTED DRAWING: None

Description

  The present invention relates to a tumor imaging agent and a tumor therapeutic agent for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is known as a type of cancer treatment. Boron neutron capture therapy, a ^{10 B-containing} compound which contains boron -10 (10 ^B) a compound which specifically accumulates in tumor cells prior to administration to a patient, the ^{10 B-containing} compound to tumor cells and normal cells This is a method of treating tumor cells by irradiating them with thermal neutrons when the accumulation ratio becomes sufficiently high and damaging tumor cells with α rays and ⁷ Li generated by the ¹⁰ B (n, α) ⁷ Li reaction. The range of α-rays and ⁷ Li generated is as short as 10 μm or less and does not fly out of the cells. Therefore, only tumor cells that have incorporated ¹⁰ B-containing compounds are damaged, and damage to normal cells with low uptake is It is said that there are few (nonpatent literature 1).

At present, L-4-borono-phenylalanine ( ¹⁰ B-L-BPA) containing ¹⁰ B is used as a ¹⁰ B-containing compound for boron neutron capture therapy. In addition, the dose (appropriate dose) of ¹⁰ B-L-BPA necessary to achieve an accumulation amount (15 ppm or more) that specifically damages only tumor cells without damaging normal cells is determined. As an imaging agent for this purpose, L-4-borono-2- ¹⁸ F-fluoro-phenylalanine ( ¹⁸ F-L-FBPA) labeled with ¹⁸ F, which is a positron emitting nuclide, is known. ¹⁸ F-L-FBPA has been shown to exhibit almost the same in vivo kinetics as ¹⁰ B-L-BPA (Non-patent Document 2). For this reason, administration of ¹⁸ FL-FBPA together with ¹⁰ B-L-BPA is expected to serve as an index for determining an appropriate dose.

Arq Bras Endocrinol Metabol, 2007, 51/5, pp. 852-856 EJNMMI Res. , 2014, 4:70

^However, since the accumulated amount of the ratio of the 10 B-L-BPA and ¹⁸ F-L-FBPA tumor cells and normal cells is only about twice, without harm to normal cells, only specific tumor cells There is a problem that it is extremely difficult to determine an appropriate dose of ¹⁰ B-L-BPA to achieve an accumulation amount that impedes the above. In addition, there is a problem that ¹⁸ F-L-FBPA is not sufficient as a tumor imaging agent due to the ratio of the accumulation amount between the low tumor cells and the normal cells.

  An object of the present invention is to provide a tumor imaging agent having a sufficiently high ratio of accumulation amount between tumor cells and normal cells. Another object of the present invention is to provide a tumor therapeutic agent for boron neutron capture therapy, which has a sufficiently high ratio of accumulation to tumor cells and normal cells.

The present invention provides a tumor imaging agent comprising a radiolabeled compound represented by the general formula (1) or a salt thereof.

In general formula (1), R ¹ represents — ¹⁸ F, — ¹¹ CH ₃ , —C ¹⁸ FH ₂ , or —C ¹⁸ FF ₂ .

  The radiolabeled compound represented by the general formula (1) or a salt thereof has a sufficiently high ratio of accumulation in tumor tissue and normal tissue (tumor tissue / normal tissue). Therefore, it is suitably used as a tumor imaging agent for imaging / visualizing accumulation of the compound and its analogs (both including salts) on tumor cells (tumor tissue).

The radiolabeled compound may be a compound represented by the general formula (2).

In General Formula (2), R ¹ represents — ¹⁸ F, — ¹¹ CH ₃ , —C ¹⁸ FH ₂ , or —C ¹⁸ FF ₂ .

The radiolabeled compound may be a compound in which R ¹ is − ¹⁸ F in the general formula (1) or the general formula (2).

Since the radiolabeled compound or a salt thereof is labeled with ¹¹ C or ¹⁸ F, it can release a positron. The emitted positron immediately combines with electrons and emits gamma rays. By measuring this γ-ray with an apparatus used for positron emission tomography (PET), the biodistribution of the radiolabeled compound or a salt thereof can be imaged quantitatively and with time. Therefore, the tumor imaging agent according to the present invention is preferably used so as to be detected by PET (for PET).

The present invention also provides a tumor therapeutic agent for boron neutron capture therapy comprising a boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof as an active ingredient.

In General Formula (3), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ .

The boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof and the radiolabeled compound represented by the general formula (1) or a salt thereof exhibit substantially the same in vivo kinetics. For this reason, the tumor therapeutic agent for boron neutron capture therapy according to the present invention is based on whether or not sufficient accumulation in the tumor to be treated is recognized by imaging and visualizing the tumor imaging agent. The applicability can be determined, and at the same time, the biodistribution of the boron ( ¹⁰ B) -containing compound can be quantitatively followed. In addition, since the boron ( ¹⁰ B) -containing compound and the tumor imaging agent have a sufficiently high accumulation ratio (tumor tissue / normal tissue) in the tumor tissue and normal tissue, the boron ( ¹⁰ B) -containing compound is appropriate. The dose range is large. Therefore, it is possible to easily determine an appropriate dose of the boron ( ¹⁰ B) -containing compound for achieving an accumulation amount that does not damage normal cells and specifically damages only tumor cells, and has side effects. Therefore, safer treatment is possible.

The boron ( ¹⁰ B) -containing compound may be a compound represented by the general formula (4).

In General Formula (4), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ .

  According to the present invention, it is possible to provide a tumor imaging agent having a sufficiently high ratio of accumulation amount between tumor cells and normal cells. According to the present invention, it is also possible to provide a tumor therapeutic agent for boron neutron capture therapy that has a sufficiently high ratio of accumulation to tumor cells and normal cells.

¹⁸ F-D-FBPA or for ¹⁸ F-L-FBPA elapsed time after administration, the accumulated amount of ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA to each organ (radioactive accumulation amount (SUV) ). ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA tumor tissue in the brain tumor-bearing rats treated with (Tumor) and ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA accumulation of normal tissue (Normal) It is a graph which shows the result of having measured the quantity (radioactive accumulation amount (SUV)). ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA administered tumor-bearing rat brain tumor tissue and normal tissue ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA accumulation amount (radioactive accumulation amount) (SUV)) is a graph showing the ratio (tumor tissue (Tumor) / normal tissue (Normal)). ¹⁸ radioactivity distribution amount of the brain slice of the tumor-bearing rats treated with F-D-FBPA or ¹⁸ F-L-FBPA a photograph imaged using an imaging plate.

  Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[Tumor imaging agent]
The radiolabeled compound according to this embodiment is represented by the following general formula (1).

In general formula (1), R ¹ represents — ¹⁸ F, — ¹¹ CH ₃ , —C ¹⁸ FH ₂ , or —C ¹⁸ FF ₂ . In this specification, when “C”, “F”, or “B” is simply described, “ ¹² C”, “ ¹⁹ F”, or “ ¹¹ B” is indicated, respectively.

Since R ¹ contains ¹¹ C or ¹⁸ F, it can emit a positron. The emitted positron combines with electrons and emits gamma rays (annihilation radiation). By detecting this γ ray, imaging becomes possible. When R ¹ contains ¹¹ C, its half-life is as short as 20 minutes, so that it is possible to perform measurement multiple times a day. When R ¹ contains ¹⁸ F, its half-life is longer than when it contains 110 minutes and ¹¹ C, so that one measurement time can be extended.

The radiolabeled compound represented by the general formula (1) may be a radiolabeled compound represented by the following general formula (2). As a result, the effect of the present invention that the ratio of the accumulation amount between tumor cells and normal cells (tumor tissue / normal tissue) is sufficiently high can be achieved more suitably.

In the general formula (2), ^{R 1} have the same meanings as in formula (1) ^{R 1} in.

The radiolabeled compound represented by the general formula (1) or the general formula (2) may be a compound in which R ¹ is ¹⁸ F, and D-4-borono- represented by the following formula (5) It may be 2- ¹⁸ F-fluoro-phenylalanine ( ¹⁸ F-D-FBPA). Thereby, the effect mentioned above is show | played much more notably.

  The salt of the radiolabeled compound is not particularly limited as long as it is pharmacologically acceptable. Examples of the salt of the radiolabeled compound include a salt with an organic acid, a salt with an inorganic acid, a salt with an organic base, and a salt with an inorganic base.

  Examples of the salt with an organic acid include acetate, trifluoroacetate, fumarate, maleate, lactate, tartrate, citrate, methanesulfonate, and the like. Examples of the salt with an inorganic acid include hydrochloride, sulfate, nitrate, hydrobromide, phosphate, and the like. Examples of the salt with an organic base include a salt with triethanolamine. Examples of the salt with an inorganic base include ammonium salt, sodium salt, potassium salt, calcium salt, magnesium salt and the like.

The radiolabeled compound and the salt thereof according to the present embodiment are, for example, a group represented by R ¹ using a D-phenylalanine derivative (for example, D-4-borono-phenylalanine, D-4-borono-phenylalanine derivative) as a starting material. Can be obtained by introducing by a known method. Specifically, for example, ¹⁸ F-D-FBPA can be obtained by reacting D-4-borono-phenylalanine with ¹⁸ F-acetyl hypofluorite.

  The tumor imaging agent according to the present embodiment is composed of the radiolabeled compound according to the present embodiment or a salt thereof. The tumor imaging agent according to the present embodiment may be provided in the form of a solution dissolved in a solvent (for example, physiological saline or any buffer) as necessary. The solution may contain other components such as a surfactant, a preservative, and a stabilizer in addition to the buffer component.

The radiolabeled compound or a salt thereof according to the present embodiment can be suitably used for tumor imaging because of a high ratio of accumulation amount between tumor cells and normal cells. In addition, since the radiolabeled compound or salt thereof according to the present embodiment is labeled with ¹¹ C or ¹⁸ F, by detecting γ-rays released by combining positrons released from the label and electrons. Tumor imaging is possible. By measuring γ-rays emitted with a positron emission tomography (PET) apparatus, the biodistribution of a radiolabeled compound or a salt thereof can be imaged quantitatively and over time. Therefore, the tumor imaging agent according to this embodiment is also suitably used as a PET probe. Since the tumor imaging agent according to the present embodiment exhibits in vivo kinetics equivalent to the boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof, the boron imaging agent represented by the general formula (3) ( ¹⁰ B) Accumulation of the compound or salt thereof in tumor cells (tumor tissue) can be accurately followed.

  The tumor to be imaged may be a malignant tumor. Moreover, there is no restriction | limiting in particular in the kind of tumor tissue used as imaging object, For example, a brain tumor, a liver tumor, a renal tumor, a lung tumor, a breast tumor, and a skin tumor are mentioned.

  Tumor imaging includes the step of administering the tumor imaging agent according to the present embodiment to a subject (administration step), and the step of detecting the radiolabeled compound or salt thereof according to the present embodiment accumulated in the tumor and surrounding tissues (detection step). ) And a step (quantitative analysis step) of quantitatively analyzing the accumulation amount of the radiolabeled compound or salt thereof according to the present embodiment in the tumor and surrounding tissues (a quantitative analysis step).

  Examples of the subject include, but are not limited to, humans, monkeys, mice, and rats. The subject is preferably a subject afflicted with a tumor.

  The method for administering the tumor imaging agent according to this embodiment to a subject is not particularly limited as long as the radiolabeled compound or salt thereof according to this embodiment reaches the tumor, but is usually intravenous administration.

  The dose of the tumor imaging agent according to this embodiment is not particularly limited as long as it is a dose sufficient to detect the radiolabeled compound or salt thereof according to this embodiment, and is appropriately determined according to the subject to be administered. You only have to set it. For example, when the radiolabeled compound or a salt thereof according to the present embodiment is detected by a PET apparatus, the dose of the tumor imaging agent according to the present embodiment (hereinafter also referred to as “administered radioactivity”) is 1 MBq / kg body weight. It may be ˜1000 MBq / kg body weight. The specific radioactivity of the tumor imaging agent according to the present embodiment may be 10 to 10,000 GBq / μmol. In addition, the administration radioactivity of the tumor imaging agent according to the present embodiment depends on the sensitivity of the PET camera used and the volume of the target individual, but in rodents (mouse, rat), approximately 200 to 500 MBq / kg body weight is 0. Administer as 1-0.5 mL saline solution. In the case of non-human primates (monkeys), 40 to 200 MBq / kg body weight is administered in 0.5 to 2 mL of physiological saline, and in the case of humans, 2 to 10 MBq / kg body weight of 1 to 5 mL of physiological saline solution. Administered as

  The method for detecting the radiolabeled compound or salt thereof according to this embodiment accumulated in the tumor and surrounding tissues is not particularly limited, and can be performed according to a known method. When detecting the radiolabeled compound or salt thereof according to the present embodiment by the PET method, for example, dynamic measurement may be performed for 60 minutes immediately after administration of the tumor imaging agent according to the present embodiment. The tumor imaging agent is administered, waits for 30 to 40 minutes, and the radiolabeled compound or salt thereof according to the present embodiment is sufficiently accumulated in the tumor and surrounding tissue, and then PET measurement may be performed for 10 to 20 minutes. .

  The method for quantitatively analyzing the accumulation amount of the radiolabeled compound or salt thereof according to the present embodiment in the tumor and surrounding tissues is not particularly limited, and can be performed according to a known method. For example, the following method is mentioned. First, the accumulated image of the radiolabeled compound or salt thereof according to the present embodiment obtained by the PET method and the morphological image of the tumor and surrounding tissue obtained by CT measurement or the like are overlapped to obtain a PET image of the tumor and surrounding tissue. Identify. Next, the region of interest is set on the PET images of the tumor and surrounding tissue, and the values normalized by the body weight and the administered radioactivity amount of the subject individual are added to the tumor and surrounding tissue according to the present embodiment. Or the amount of accumulated salt.

[Tumor therapeutic agent for boron neutron capture therapy]
The tumor therapeutic agent for boron neutron capture therapy according to the present embodiment includes a boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof as an active ingredient.

In General Formula (3), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ .

The boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof exhibits substantially the same in vivo kinetics as the radiolabeled compound represented by the general formula (1) or a salt thereof, The ratio of accumulation in the tissue (tumor tissue / normal tissue) is sufficiently high. For this reason, there is a wide range of appropriate doses to achieve an accumulation amount that does not damage normal cells and specifically damages only tumor cells, and it is easy to determine the appropriate dose, Therefore, safer treatment is possible.

Boron represented by the general formula (3) ⁽¹⁰ B) containing compound may be boron ⁽¹⁰ B) containing a compound represented by the following general formula (4). As a result, the effect of the present invention that the ratio of the accumulation amount between tumor cells and normal cells (tumor tissue / normal tissue) is sufficiently high can be achieved more suitably.

In General Formula (4), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ .

Boron represented by the general formula (3) ⁽¹⁰ B) containing compound may be boron ⁽¹⁰ B) containing a compound represented by the following formula (6).

The boron ( ¹⁰ B) -containing compound represented by the formula (6) is a known compound also referred to as D-4-borono-phenylalanine ( ¹⁰ BD-BPA), and a commercially available product may be used. .

The salt of the boron ( ¹⁰ B) -containing compound is not particularly limited as long as it is pharmacologically acceptable, and examples thereof include those exemplified as the salt of the radiolabeled compound.

The boron ( ¹⁰ B) -containing compound and its salt according to this embodiment can be obtained by a method according to the radiolabeled compound and its salt according to this embodiment.

The boron neutron capture therapy tumor therapeutic agent according to the present embodiment may include the above-described boron ( ¹⁰ B) -containing compound or a salt thereof alone or in combination of two or more. May be.

  The therapeutic agent for boron neutron capture therapy according to this embodiment may be provided in the form of a solution dissolved in a solvent (for example, physiological saline or any buffer solution) as necessary. The solution may contain other components such as a surfactant, a preservative, and a stabilizer in addition to the buffer component.

  The tumor treatment method using the tumor therapeutic agent for boron neutron capture therapy according to this embodiment can be carried out according to so-called boron neutron capture therapy.

The tumor therapeutic agent for boron neutron capture therapy according to this embodiment may further include the tumor imaging agent according to the present invention. Thus, it is possible to more accurately grasp the integrated amount of the boron ^{(10 B)} containing compound or tumor tissue of a salt thereof in the individual patient. Specifically, the tumor imaging agent is mixed with the tumor therapeutic agent and co-administered, and the radioactivity of the tumor tissue measured after a certain period of time is calculated in advance, the weight of the tumor therapeutic agent and the radioactivity of the tumor imaging agent. By calculating backward from the ratio, the amount of tumor therapeutic agent accumulated in the tumor tissue can be quantitatively measured.

When the tumor therapeutic agent for boron neutron capture therapy according to the present embodiment includes the tumor imaging agent according to the present invention, the total amount of the boron ( ¹⁰ B) -containing compound and its salt in the tumor therapeutic agent and the tumor imaging according to the present invention The ratio to the amount of the agent is, for example, that the total amount of the boron ( ¹⁰ B) -containing compound and its salt in the tumor therapeutic agent is 100 mg to 5,000 mg (weight basis) with respect to the tumor imaging agent of 2 to 10 MBq / kg body weight. ), And preferably 500 mg to 1,500 mg (by weight).

  Hereinafter, based on an Example, this invention is demonstrated more concretely. However, the present invention is not limited to these.

[Test Example 1: Production of PET probe]
(1) Production of ¹⁸ F-D-FBPA Using an F-1 synthesizer (manufactured by Sumitomo Heavy Industries, Ltd.) according to the method described in Non-Patent Document 2, ¹⁸ F-D-FBPA Manufactured. Specifically, ¹⁸ F-acetyl hypofluorite was first bubbled into trifluoroacetic acid (5 mL) containing 30 mg of 4-borono-D-phenylalanine at a rate of 600 mL / min at room temperature. Next, trifluoroacetic acid was removed while flowing nitrogen gas at a flow rate of 200 mL / min under reduced pressure. The residue was dissolved in 3 mL of 0.1% acetic acid, and the FBPA fraction (retention time 19-21 minutes) was separated and recovered from the resulting solution using high performance liquid chromatography (HPLC). The HPLC conditions are as follows.
Column: YMC-Pack ODS-A (inner diameter 20 mm, column length 150 mm, manufactured by YMC Co., Ltd.)
Mobile phase: 0.1% acetic acid Flow rate: 10 mL / min Detector: UV detector (280 nm) and radiation detector After the collected FBPA fraction was dried, the residue was dissolved in physiological saline, and ¹⁸ F- A D-FBPA sample was used. The radiochemical purity of the obtained ¹⁸ FD-FBPA was 98% or more, and the specific activity was 28.3 ± 1.8 GBq / μmol.

^{(2) 18 F-L-} FBPA instead producing 4-borono -D- phenylalanine, except for using 4-borono -L- phenylalanine, in the same manner as in ^(1), 18 F-L- An FBPA sample was obtained. The radiochemical purity of the obtained ¹⁸ FL-FBPA was 98% or more, and the specific activity was 26.4 ± 3.7 GBq / μmol.

[Test Example 2: Evaluation of kinetics of ¹⁸ FD-FBPA in major organs and urine]
Normal rats administered with ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA were used to measure radioactivity dynamics in major organs and urine. First, 5 MBq of ¹⁸ F-D-FBPA sample or ¹⁸ F-L-FBPA sample was administered as a bolus from the tail vein of normal rats, and the rats were dissected 10 minutes, 30 minutes, 60 minutes and 90 minutes after administration, and blood, Brain, liver, and bladder (urine) were collected. For each collected organ, organ weight and radioactivity were measured. The value obtained by normalizing the measured radioactivity with the organ weight and the dose radioactivity was defined as the accumulation amount of ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA (radioactivity accumulation amount (SUV)) in each organ. (Each group, 5 rats).

FIG. 1 shows each organ (Brain, Liver, Blood, Bladder) with respect to the time elapsed after administration of ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA. ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA accumulation amount (radioactivity accumulation amount (SUV)). In FIG. 1, the letter D or L given to each organ means the amount of ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA accumulated. As shown in FIG. 1, ¹⁸ F-D-FBPA was found to be excreted from the blood through the kidneys and into the urine very quickly as compared with ¹⁸ F-L-FBPA. This indicates that ¹⁸ FD-FBPA is advantageous in reducing the background.

[Test Example 3: Evaluation of accumulation of ¹⁸ FD-FBPA in tumor]
¹⁸ using the F-D-FBPA or ¹⁸ tumor-bearing rats treated with F-L-FBPA, it was measured radioactive accumulation in tumor tissues and normal tissues of the brain. First, rats 2 weeks after transplantation of cancer cells (C-6 glioma) into the hemisphere of the brain were used. While anesthetizing the cancer-bearing rat with 1.5-2.0% isoflurane (diluted gas: oxygen), brain morphological images were collected with a small animal X-CT apparatus (ClairvivoCT, manufactured by Shimadzu Corporation). With anesthesia, the tumor-bearing rats were fixed in the gantry of an animal PET apparatus (SHR-38000, manufactured by Hamamatsu Photonics Co., Ltd.). After 15 minutes transmission measurement for absorption correction, 20MBq of ¹⁸ F-D-FBPA sample or ¹⁸ F-L-FBPA sample was administered as a bolus from the tail vein of rats, and 90 minutes emission measurement was performed. did. After the PET measurement was completed, the PET integrated image of the brain 20 to 40 minutes after administration of ¹⁸ F-D-FBPA sample or ¹⁸ F-L-FBPA sample was superimposed on the brain CT image. Regions of interest were set on PET images of tumor tissue and normal brain tissue identified from X-CT images, and the values normalized by the weight of each individual and the amount of radioactivity administered were obtained by applying ¹⁸ FD-FBPA to each site. Or it was set as the accumulation amount (radioactivity accumulation amount (SUV)) of ¹⁸ FL-FBPA (each group, 5 rats). In addition, after the PET measurement was completed, the brain was excised to create a section, and the radioactivity distribution was imaged using an imaging plate (Fuji Film Co., Ltd.).

The results of PET measurement are shown in FIGS. FIG. 2 shows ¹⁸ F-D-FBPA or ¹⁸ F-L applied to tumor tissue (Tumor) and normal tissue (Normal) of a tumor-bearing rat brain administered with ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA. -It is a graph which shows the result of having measured the accumulation amount (radioactive accumulation amount (SUV)) of FBPA. ^3, the accumulated amount of 18 F-D-FBPA or ^{18 18} of the F-L-FBPA to tumor tissues and normal tissues of the brain tumor-bearing rats treated with F-D-FBPA or ¹⁸ F-L-FBPA ( It is a graph which shows ratio (tumor tissue (Tumor) / normal tissue (Normal)) of radioactivity accumulation amount (SUV). As shown in FIG. ^2, 18 accumulation property itself F-D-FBPA into tumor ^tissue, 18 F-L-FBPA but was about one third of, as shown in FIGS. 2 and ^{3, 18} F -D-FBPA has extremely low accumulation in normal tissues, and the ratio of accumulation in tumor tissues and normal tissues (tumor tissues / normal tissues) was 4 times higher than that in ¹⁸ F-L-FBPA .

FIG. 4 is a photograph obtained by imaging an amount of radioactivity distribution in a brain section of a tumor-bearing rat administered with ¹⁸ F-D-FBPA or ¹⁸ F-L-FBPA using an imaging plate. ^{Although both 18} FD-FBPA and ¹⁸ FL-FBPA accumulated in the tumor tissue (black dark portion indicated by an arrow in the figure), ¹⁸ FL-FBPA became normal tissue. However, ¹⁸ FD-FBPA was extremely low in normal tissue (reflected in the difference in the degree of blackness in portions other than the tumor tissue in the figure).

Claims (6)

A tumor imaging agent comprising a radiolabeled compound represented by the general formula (1) or a salt thereof.

[In the general formula (1), ^{R _{1, - 18 F, - 11 CH}} 3, showing a ^-C 18 FH _2, or ^-C 18 FF _2. ] The tumor imaging agent according to claim 1, wherein the radiolabeled compound is a compound represented by the general formula (2).

[In the general formula (2), ^{R _{1, - 18 F, - 11 CH}} 3, showing a ^-C 18 FH _2, or ^-C 18 FF _2. ] R ¹ is ^{- 18} is F, tumor imaging agent according to claim 1 or 2.   The tumor imaging agent according to any one of claims 1 to 3, which is used for positron emission tomography (PET). A tumor therapeutic agent for boron neutron capture therapy comprising a boron ( ¹⁰ B) -containing compound represented by the general formula (3) or a salt thereof as an active ingredient.

[In General Formula (3), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ . ] The boron therapeutic agent for boron neutron capture therapy according to claim 5, wherein the boron ( ¹⁰ B) -containing compound is a compound represented by the general formula (4).

[In General Formula (4), R ² represents —H, —F, —CH ₃ , —CFH ₂ , or —CF ₃ . ]