Diagnostic agent for pancreatic function

Abstract

The present application relates to a method for diagnosing pancreatic function, comprising: a step of administering to a subject a diagnostic agent for pancreatic function containing a compound represented by general formula (1-0) as an effective ingredient; a step of detecting the compound (1-0) accumulated in the pancreas; and a step of quantitatively analyzing the amount of the compound (1-0) accumulated in the pancreas. [In general formula (1-0), R represents -O(CH2) n -, -O(CH2) n OC2H4-, -CH2O(CH2) n - or -CH2O(CH2) n OC2H4-, n represents an integer of 1 to 5, and Q 1 represents F or -OCH3.]

Description

Technical Field

[0001] This invention relates to diagnostic agents for pancreatic function. Background Technology

[0002] The pancreas has exocrine functions, secreting amylase (for carbohydrates), trypsin (for protein breakdown), and pancreatic juice (containing lipase for fat breakdown), as well as endocrine functions, secreting hormones such as insulin and glucagon, necessary for glucose metabolism. Therefore, if pancreatic dysfunction occurs, the body cannot produce or absorb the energy needed for survival from food. Insufficient nutrient supply to cells leads to decreased function of various organs. Furthermore, even though early detection and treatment of cancer are now common, pancreatic cancer is frequently diagnosed late, resulting in a 5-year survival rate of less than 10%, making it one of the most difficult-to-treat cancers.

[0003] Previously, in the diagnosis of pancreatic diseases such as acute pancreatitis, chronic pancreatitis, and early-stage pancreatic cancer, imaging diagnostics based on X-ray-CT and MRI, as well as diagnostics based on endoscopic ultrasound, were used (e.g., Non-Patent Literature 1 and Non-Patent Literature 2). On the other hand, Non-Patent Literature 3 discloses the use of PET probes in patients with type II diabetes. 18 The introduction of F]FDG into the pancreas is increased.

[0004] Existing technical documents

[0005] Non-patent literature

[0006] Non-patent literature 1: Journal of the Japanese Society for Abdominal Emergency Medicine, 2008, Vol. 28, pp. 561-571.

[0007] Non-patent literature 2: Journal of the Pancreas, 2009, Vol. 10, pp. 280-283. Non-patent literature 3: PLoS ONE, 2019, Vol. 14, e0213202. Summary of the Invention

[0008] [The problem the invention aims to solve]

[0009] Previous X-ray-CT or MRI-based imaging diagnostics relied on information about structural changes in organs, such as pancreatic atrophy or calcification, and therefore could not detect prior biological functional changes. This is also true for endoscopic ultrasound-based diagnostics. Furthermore, endoscopic ultrasound-based diagnostics is a more invasive procedure. Additionally, the method disclosed in Non-Patent Literature 3 involves... 18 FDG, as a probe in PET examination, can only evaluate an increase in the accumulation of inflammation in organs.

[0010] Therefore, an object of the present application is to provide a diagnostic agent for pancreatic function capable of early diagnosis of a change in function of the pancreas.

[0011] [Means for solving the problem]

[0012] The present application relates to a diagnostic agent for pancreatic function using a compound represented by General Formula (1-0) (hereinafter also referred to as "compound (1-0)") as an effective ingredient.

[0013]

[0014] In General Formula (1-0), R represents -O(CH2) n -, -O(CH2) n OC2H4-, -CH2O(CH2) n - or -CH2O(CH2) n OC2H4-, n represents an integer of 1 to 5, and Q 1 represents F or -OCH3.

[0015] It is known that the compound (1-0) is useful for detection of mitochondrial complex-I (hereinafter, also referred to as "MC-I"). The diagnostic agent for pancreatic function of the present application is accumulated in the pancreas, and further becomes an accumulated amount in proportion to the MC-I activity of the pancreas, and thus is suitable for use in diagnostic use of pancreatic function. In addition, as shown in the examples described later, a decrease in the MC-I activity of the pancreas occurs prior to deterioration of a biochemical index (for example, an increase in glucose concentration in blood). Therefore, the diagnostic agent of the present application can early diagnose a change in function of the pancreas.

[0016] Q of the above-described diagnostic agent 1 may be 18 F or -O 11 CH3. By this, the above-described compound can emit a positron. The positron emitted from the above-described compound immediately combines with an electron to emit a gamma ray (annihilation radiation). By measuring this gamma ray using a device used in positron emission tomography (PET method), the above-described compound accumulated in the pancreas can be imaged quantitatively and chronologically. That is, it can also be used as a marker compound for the PET method.

[0017] In addition, the present application can also be understood as a diagnostic method for pancreatic function including the steps of: administering the above-described diagnostic agent to a subject; detecting the compound (1-0) accumulated in the pancreas; and quantitatively analyzing the accumulated amount of the compound (1-0) in the pancreas.

[0018] This invention can also be understood as the use of compounds of general formula (1-0) for use in the diagnosis of pancreatic function. Furthermore, this invention can also be understood as the use of compounds of general formula (1-0) in the manufacture of diagnostic agents for pancreatic function.

[0019] [Invention Effects]

[0020] According to the present invention, a diagnostic agent for pancreatic function that can diagnose early changes in pancreatic function can be provided. Attached Figure Description

[0021] Figure 1 It is about [ 18 The accumulation of F]BCPP-BF in the pancreas was plotted as a curve of the radioactive energy accumulation (SUV) measured by PET versus the radioactive energy accumulation (SUV) measured by dissection.

[0022] Figure 2 This represents the pancreatic [expression] measured using healthy (Lean) and obese (Fatty) rats at various ages. 18 The introduction of F]BCPP-BF (SUV) Figure 2 (A)), pancreas weight ( Figure 2 (B) and blood glucose concentration ( Figure 2 (C)) is a graph of the results.

[0023] Figure 3 It indicates that it is directed towards the pancreas. 18 A graph showing the relationship between the introduction of BCPP-BF (SUV) and blood glucose or triglyceride concentration.

[0024] Figure 4 (A) is a graph representing the number of insulin-positive cells per unit area of ​​the pancreas in 5-week-old and 16-week-old rats. Figure 4 (B) represents the pancreatic [development] of 16-week-old rats (healthy (Lean) rats and obese (Fatty) rats. 18 A graph showing the relationship between the introduction of F]BCPP-BF (SUV) and the number of insulin-positive cells per unit area. Detailed Implementation

[0025] The following describes in detail the methods for implementing the present invention. However, the present invention is not limited to the following embodiments.

[0026] The diagnostic agent for pancreatic function in this embodiment uses the compound represented by general formula (1-0) as the active ingredient.

[0027]

[0028] in the compound (1-0), R is -O(CH2) n - or -O(CH2) n OC2H4-, -CH2O(CH2) n - or -CH2O(CH2) n OC2H4-. R is preferably -O(CH2) n - or -O(CH2) n OC2H4-, more preferably -O(CH2) n -.

[0029] In the compound (1-0), n is an integer of 1 to 5, preferably an integer of 2 to 5, more preferably an integer of 3 to 5, further preferably 4.

[0030] In the compound (1-0), Q 1 is F or -OCH3, preferably 18 F or -O 11 CH3. Q 1 is 18 F or -O 11 CH3. The compound (1-0) in which Q 1 is -O 11 CH3can emit a positron, and is therefore suitable as a labeling compound (PET probe) used in PET method. In addition, in the case where Q 1 is 18 F, the half-life is longer than -O 11 CH3, and therefore the measurement time can be prolonged.

[0031] The bonding position of the -OCH2- bound to the pyridazine ring and the bonding position of R in the pyridine ring are not particularly limited, and preferably the bonding position of the -OCH2- bound to the pyridazine ring is the 5-position of the pyridine ring, and the bonding position of R is the 2-position of the pyridine ring. The compound represented by the general formula (1-0') shown below (hereinafter, also referred to as "compound (1-0')") is a structural formula in which the bonding position of the -OCH2- bound to the pyridazine ring is the 5-position of the pyridine ring, and the bonding position of R is the 2-position of the pyridine ring.

[0032]

[0033] In the general formula (1-0'), R, n and Q 1 have the same meanings as R, n and Q 1 in the general formula (1-0).

[0034] Since it is more suitable for diagnostic use of pancreatic function, the compound (1-0) is preferably a compound represented by General Formula (1-0") (hereinafter, also referred to as "compound (1-0")"), more preferably a compound represented by Formula (1) (hereinafter, also referred to as "compound (1)").

[0035]

[0036] In General Formula (1-0"), n and Q 1 are the same as n and Q in General Formula (1-0). 1 are the same as n and Q in General Formula (1-0).

[0037]

[0038] In Formula (1), Q 1 is the same as Q in General Formula (1-0). 1 are the same as n and Q in General Formula (1-0).

[0039] The compound (1-0) can be synthesized, for example, from a corresponding precursor. The same applies to the compound (1-0'), the compound (1-0"), and the compound (1).

[0040] As the corresponding precursor of the compound (1-0), for example, a compound represented by General Formula (2-0) (hereinafter, also referred to as "compound (2-0) can be given. As the corresponding precursor of the compound (1-0'), the compound (1-0"), and the compound (1), for example, a compound in which R and the bonding position of the -OCH2- of the pyridine ring combined with the pyridazine ring and the bonding position of R in the compound (2-0) are the same as those of the compound (1-0'), the compound (1-0"), and the compound (1) can be given.

[0041]

[0042] In General Formula (2-0), R is the same as R in General Formula (1-0). Q 2 represents a dissociable substituent (a substituted sulfonyloxy group, a halogen atom, or a hydroxyl group, etc.).

[0043] As the substituted sulfonyloxy group, for example, a tosyl oxy group (-OTs), a methanesulfonyloxy group (-OMs), a trifluoromethanesulfonyloxy group (-OTf), a nitrobenzenesulfonyloxy group (-ONs) can be given, and -OTs is preferably used.

[0044] As the halogen atom, fluorine, chlorine, bromine, iodine can be given.

[0045] The precursor can be synthesized, for example, by the method described in International Publication No. 2014 / 30709.

[0046] The compound (1-0) accumulates in the pancreas with MC-I specificity, and thus the amount of accumulation changes in correlation with the degree of pancreatic function. That is, if the function of the pancreas decreases, the amount of accumulation of the compound (1-0) decreases, and if the function of the pancreas is enhanced, the amount of accumulation of the compound (1-0) increases. Therefore, the diagnostic agent according to the present embodiment is suitably used for the diagnosis of pancreatic function by measuring the amount of accumulation of the compound (1-0).

[0047] The measurement of the amount of accumulation of the compound (1-0) is not limited thereto, and for example, a labeled compound can be prepared by labeling with a fluorescent dye or the like, or by labeling with a single photon nuclide (Tc, etc.) or a positron nuclide, and the measurement is performed by detecting the label. 123 I, 99m Tc, etc.) or a positron nuclide. The positron labeling can be performed by, for example, setting Q 1 to -O 11 CH3or 18 F. In the case of positron labeling, the in vivo distribution of the compound (1-0) can be imaged quantitatively and chronologically by measuring annihilation radiation with a device used in PET.

[0048] The diagnostic agent of the present embodiment can be produced, for example, by dissolving the compound (1-0) in an arbitrary buffer. In this case, the diagnostic agent of the present embodiment is provided as a solution, and can contain other components such as a surfactant, a preservative, a stabilizer, and the like in addition to the buffer component.

[0049] The diagnostic method of pancreatic function according to the present embodiment includes a step of administering the diagnostic agent of the present application to a subject, a step of detecting the compound (1-0) accumulated in the pancreas, and a step of quantitatively analyzing the amount of accumulation of the compound (1-0) in the pancreas.

[0050] As the subject, for example, a human, a mouse, and a rat can be mentioned, but the present application is not limited thereto.

[0051] The method of administering the diagnostic agent to the subject is not particularly limited as long as the compound (1-0) reaches the pancreas, and is typically intravenous administration.

[0052] The amount of administration of the diagnostic agent is not particularly limited as long as it is an amount sufficient to detect the compound (1-0) in the pancreas, and can be appropriately set in accordance with the subject to be administered and the method of detecting the compound (1-0). For example, in the case of using a compound (1-0) in which Q 1 is 18 F or -O 11The amount of the diagnostic agent of the compound (1-0) to be administered (hereinafter, also referred to as "administered radioactivity") can be 1 to 1000 MBq / kg body weight in the case where the compound (1-0) is detected using an apparatus used in the PET method. The specific radioactivity of the compound (1-0) is 10 to 10,000 GBq / μmol. In addition, the administered radioactivity of the diagnostic agent depends on the sensitivity of the PET camera used and the volume of the subject individual, but in rodents (mice, rats), about 200 to 500 MBq / kg body weight is administered in 0.1 to 0.5 mL of physiological saline. In the case of non-human primates (apes), 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 is administered in 1 to 5 mL of physiological saline.

[0053] As a method for detecting the compound (1-0) accumulated in the pancreas, there is no particular limitation, and it can be performed according to a publicly known method. For example, in the case where a compound (1-0) containing Q 1 For 18 F or -O 11 In the case of the diagnostic agent of the compound (1-0), the compound (1-0) can be detected by the PET method. The measurement method in the PET method is not particularly limited, and it can be performed according to a publicly known method. In addition, for example, as a method for measurement using the PET method, dynamic measurement can be performed for 60 minutes from immediately after administration of the diagnostic agent, or the diagnostic agent can be administered, and after waiting for 30 to 40 minutes so that the compound (1-0) is sufficiently accumulated in the pancreas, PET measurement can be performed for 10 to 20 minutes.

[0054] As a method for quantitatively analyzing the accumulation amount of the compound (1-0) in the pancreas, there is no particular limitation, and it can be performed according to a publicly known method. For example, the following methods can be given. First, the accumulation image of the compound (1-0) obtained by the PET method is superimposed on the morphological image of the pancreas obtained by CT measurement or the like, and the PET image of the pancreas is identified. Next, a region of interest is set on the PET image of the pancreas, and the value normalized by the body weight of the individual to be the object and the administered radioactivity is taken as the accumulation amount of the compound (1-0) in the pancreas. In addition, instead of the morphological image of the pancreas, an image obtained by the PET method using a probe capable of detecting the pancreas can be used.

[0055] The diagnostic method according to the present embodiment can further include a step of diagnosing the function of the pancreas by comparing the quantitatively analyzed accumulation amount of the compound (1-0) with a reference value.

[0056] The reference value can be appropriately set according to the purpose of diagnosis. For example, in the case where the diagnostic method of the present embodiment is implemented in a group health diagnosis, the reference value can also be a normal range decided in advance from the distribution of the accumulation amount of the compound (1-0) in a plurality of the same subjects. In this case, it is possible to diagnose whether or not the pancreatic function in a specific subject is normal or not, depending on whether or not the quantitative analysis value of the accumulation amount in the specific subject falls within the normal range.

[0057] In addition, for example, in the case where the diagnostic method of the present embodiment is implemented in a subject having a symptom that causes dysfunction of the pancreas (e.g., diabetes, abnormality of lipid metabolism, chronic pancreatitis, acute pancreatitis, pancreatic cancer, etc.) in order to perform follow-up observation of the symptom, confirmation of the treatment effect, or prognosis prediction, etc., the reference value can also be a measurement result of the accumulation amount of the compound (1-0) in the subject at a certain time point (e.g., at the time of health, at the time of initial diagnosis, at the time of start of treatment, at the time of end of treatment, etc.).

[0058] The above-described present application can also be understood as the compound represented by General Formula (1-0) used in the diagnosis of pancreatic function. The diagnosis of pancreatic function can be implemented, for example, by the method exemplified in the above-described diagnostic method of pancreatic function.

[0059] [Examples]

[0060] Hereinafter, the present application will be more specifically described based on examples. However, the present application is not limited to these.

[0061] [Example 1: Synthesis of PET probe]

[0062] The compound represented by the following formula was synthesized by the method described in Non-Patent Literature (J. Labelled Comp. Radiopharm., 2013, Vol. 56, No. 11, pp. 553-561). 18 F]BCPP-BF was synthesized by the method described in Non-Patent Literature (J. Labelled Comp. Radiopharm., 2013, Vol. 56, No. 11, pp. 553-561). The radiochemical purity of the obtained final product was 100.0%, and the specific radioactivity was 74.5 GBq / μmol.

[0063]

[0064] In addition, in order to determine the position of the pancreas, a probe (D-[ 11 C]MT) that recognizes an amino acid transporter (LAT-1) that is highly expressed in the pancreas of a small animal was prepared. 11 C]MT was synthesized by the method described in Example 1 of International Publication No. 2005 / 115971. The radiochemical purity of the obtained final product was 100.0%, and the specific radioactivity was 56.4 GBq / μmol.

[0065] [Experimental Example 2: Evaluation of pancreatic function in a type II diabetes model rat]

[0066] (Type II diabetes model rat)

[0067] Male Zucker Leprfa / Leprfa rats (hereinafter, also referred to as "Fatty rats") which are pathologically similar to human type II diabetes, and male Zucker Leprfa / + rats (hereinafter, also referred to as "Lean rats") which are a control thereof, were subjected to PET measurement at 5 weeks of age, 8 weeks of age, 16 weeks of age, and 26 weeks of age.

[0068] (PET measurement)

[0069] The rats were anesthetized with isoflurane and fixed in the gantry of an animal PET camera (SHR-38000, manufactured by Hamamatsu Photonics K.K.). After transmission measurement for 15 minutes for absorption correction, about 20 MBq / 0.5 mL of D-[ 11 C]MT was administered from the tail vein of the rat, and emission measurement was performed for 60 minutes. Subsequently, about 20 MBq / 0.5 mL of [ 18 F]BCPP-BF was administered from the tail vein of the rat, and emission measurement was performed for 60 minutes. After the PET measurement, the pancreatic tissue identified from the PET accumulation image 40 to 60 minutes after the administration of D-[ 11 C]MT was set as a region of interest, and the accumulation amount of [ 18 F]BCPP-BF to the region of interest was calculated. Subsequently, the calculated accumulation amount was normalized by the body weight of each individual and the administered radioactivity, and the accumulation amount of [ 18 F]BCPP-BF to the pancreas (radioactivity accumulation amount (SUV)) was obtained.

[0070] (Determination of radioactivity accumulation amount (SUV) by dissection)

[0071] Immediately after the PET measurement, the pancreas was removed from the rat, and the weight of the removed pancreas was measured. Subsequently, the radioactivity of the removed pancreas was measured using a gamma counter (manufactured by Perkin Elmer, 1480 WIZARD). The measured radioactivity was normalized by the body weight of the rat, the weight of the pancreas, and the administered radioactivity, and the radioactivity accumulation amount (SUV) by dissection was calculated.

[0072] (Determination of blood glucose concentration and blood neutral fat concentration)

[0073] Blood was collected from rats immediately after PET measurement to determine blood glucose and triglyceride concentrations. Blood glucose and triglyceride concentrations were measured using an automated biochemical analyzer (Hitachi High-Tech Corporation 7180).

[0074] (Determination of the number of insulin-positive cells)

[0075] The number of insulin-positive cells (cells / μm) was determined by immunostaining using the removed pancreas after measuring its weight and radiation energy. 2 Specifically, an anti-insulin monoclonal antibody (manufactured by Nichirei Biosciences, K36aC10) was used as the primary antibody, and a secondary antibody was used... Pancreatic tissue sections were stained with MAX-PO(M) (manufactured by Nichirei Biosciences) and DAB (manufactured by DOJINDO, D006) as a chromogenic agent. Five islets were randomly selected from the tissue sections, and the islets were photographed at 100x magnification using an optical microscope (manufactured by OLYMPUS, BX41) and a microscope camera (manufactured by OLYMPUS, DP22). The number of insulin-positive cells (cells / μm) was determined using dedicated image software (manufactured by OLYMPUS, cellSensV1.15). 2 ).

[0076] (result)

[0077] Figure 1 It is directed towards the pancreas. 18 The accumulation of F]BCPP-BF was plotted against the radioactive energy accumulation (SUV) measured by dissection, and a graph of the radioactive energy accumulation (SUV) measured by PET was also plotted. Figure 1 As shown, SUVs measured by PET and SUVs measured by dissection show a good correlation (R0). 2 =0.777, p<0.001). It can be seen that [[...]] 18 F]BCPP-BF performs non-invasive MC-I measurements of the pancreas. The following... Figures 2 to 4 The image shows the direction towards the pancreas. 18 The introduction of F]BCPP-BF (SUV) is the amount of radioactive energy stored (SUV) measured by PET.

[0078] Figure 2 This indicates that the pancreas was measured using healthy (Lean) and obese (Fatty) rats of various ages. 18 The introduction of F]BCPP-BF (SUV) Figure 2 (A)), pancreas weight (Figure 2 (B) and blood glucose concentration Figure 2 (C). In Figure 2 In the figure, "★" indicates that the difference between the data of the Fatty rats and the data of the Lean rats was statistically significant (p<0.05).

[0079] As shown in Figure 2 (B), in the Fatty rats, hypertrophy of the pancreas was confirmed at the time of 8 weeks of age, and thereafter, atrophy of the pancreas was confirmed. In addition, as shown in Figure 2 (C), in the Fatty rats, abnormality of the blood glucose concentration was detected after 16 weeks of age. On the other hand, as shown in Figure 2 (A), in the Fatty rats, the uptake of 18 F] BCPP-BF into the pancreas decreased after 5 weeks of age. The decrease in the uptake of 18 F] BCPP-BF into the pancreas means the decrease in the MC-I activity of the pancreas. From these results, it was found that the decrease in the pancreatic function could be detected by the PET measurement using 18 F] BCPP-BF before the abnormality of the blood glucose concentration was detected (at 5 weeks and 8 weeks of age).

[0080] Figure 3 is a graph showing the relationship between the uptake of 18 F] BCPP-BF into the pancreas (SUV) and the blood glucose concentration or the blood neutral fat concentration. Figure 3 (A) is a graph plotting the blood glucose concentration and the uptake of 18 F] BCPP-BF into the pancreas (SUV) in the rats at 5 weeks of age (Lean rats and Fatty rats). Figure 3 (B) is a graph plotting the blood neutral fat concentration and the uptake of 18 F] BCPP-BF into the pancreas (SUV) in the rats at 5 weeks of age (Lean rats and Fatty rats). Figure 3 (C) is a graph plotting the blood glucose concentration and the uptake of 18 F] BCPP-BF into the pancreas (SUV) in the rats at 16 weeks of age (Lean rats and Fatty rats). Figure 3 (D) is a graph plotting the blood neutral fat concentration and the uptake of 18 F] BCPP-BF into the pancreas (SUV) in the rats at 16 weeks of age (Lean rats and Fatty rats).

[0081] It has been reported that high glucose concentration in blood or high concentration of neutral fat in blood induces pancreatic dysfunction (e.g., FEBS J., 2013, Vol. 280, pp. 1039-1050; Endocr Rev., 2008, Vol. 29, pp. 351-366; Kidney Int., 2006, Vol. 70, pp. 1560-1566). As shown in Figure 3 , it is possible to use 18 F]BCPP-BF to detect this phenomenon as impairment of MC-I activity.

[0082] Figure 4 (A) is a graph showing the number of insulin-positive cells per unit area of the pancreas of rats at 5 weeks of age and 16 weeks of age. Figure 4 In (A), the white bars indicate the results of healthy (Lean) rats, and the black bars indicate the results of obese (Fatty) rats. Figure 4 (B) is a graph showing the relationship between the import (SUV) of 18 F]BCPP-BF into the pancreas and the number of insulin-positive cells per unit area in rats at 16 weeks of age (healthy (Lean) rats and obese (Fatty) rats).

[0083] As shown in Figure 4 (A), the number of insulin-positive cells, which is an index of existing pancreatic function, was counted by immunostaining, and as a result, no significant difference was found between healthy (Lean) rats and obese (Fatty) rats at 5 weeks of age, and a significant decrease was detected in obese (Fatty) rats at 16 weeks of age. Note that, as shown in Figure 2 (A), in the PET measurement method using 18 F]BCPP-BF, a decrease in MC-I activity of the pancreas in obese (Fatty) rats was detected at the time of 5 weeks of age.

[0084] As shown in Figure 4 (B), in rats at 16 weeks of age (healthy (Lean) rats and obese (Fatty) rats), the MC-I activity of the pancreas (import (SUV) of 18 F]BCPP-BF into the pancreas) measured by the PET measurement method using 18 F]BCPP-BF showed a significant positive correlation (R 2 = 0.649, p = 0.001) with the number of insulin-positive cells per unit area.

Claims

1. The use of the compound represented by general formula (1-0′) in the manufacture of a diagnostic agent for pancreatic function based on MC-I activity, wherein, In the general formula (1-0′), R represents -O(CH2). n -、-O(CH2) n OC2H4-、-CH2O(CH2) n -or -CH2O(CH2) n OC2H4-, where n represents an integer from 1 to 5, and Q 1 It represents F or -OCH3.

2. The use according to claim 1, wherein, The compound is a compound represented by the general formula (1-0″). In the general formula (1-0″), n and Q 1 With respect to n and Q in general formula (1-0′) 1 They have the same meaning.

3. The use according to claim 1, wherein, The compound is the compound represented by the following formula (1). In equation (1), Q 1 Q in general formula (1-0′) 1 They have the same meaning.

4. The use according to any one of claims 1 to 3, wherein, Q 1 for 18 F or -O 11 CH3.

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