JP2000281591A - Image diagnostic probe for amyloid-accumulating disease with basic blue-41 and palatine fast black wan and image diagnostic composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a compound or its salt or solvate that comprises Basic blue-41 and Palatine fast black WAN and is useful as an image diagnostic probe for amyloid-accumulating diseases since it has the coupling specificity to β-amyloid protein and high blood-brain barrier permeability. SOLUTION: This probe is a compound selected from the group consisting of Basic blue-41 and Palatine fast black WAN or its salts or solvates and is preferably labeled with a radioactive nuclide. This compound is preferably labeled with a proton-radiative nuclide selected from the group consisting of 11C, 13N, 15O and 18F. The Basic blue-41 is represented by formula I, while Palatine fast black WAN is represented by formula II. These compounds can be administered topically and systemically and preferably, intradermally, interperitoneally or the like. The radiation dose of this compound is preferably 18-740 megabecquerel.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a probe for diagnostic imaging of a disease in which amyloid is accumulated, in particular, a probe labeled with a positron emitting nuclide, and a diagnostic imaging composition containing the probe.

[0002]

BACKGROUND OF THE INVENTION Amyloid-accumulating diseases include various diseases characterized by the deposition of insoluble fibrillar proteins (amyloid) on various organs and tissues in the body, including Alzheimer's disease and Down's syndrome. It is. Of these, Alzheimer's disease (AD) is currently regarded as one of the most difficult diseases to treat, and accurate early diagnosis is desired. Alzheimer's disease is a disease characterized by progressive dementia that occurs mainly from the old age to the old age. Pathologically, it is characterized by general atrophy of the cerebrum, marked degeneration and loss of nerve cells, neurofibrillary tangles and the appearance of senile plaques. It is known that the greatest risk factor of dementia represented by Alzheimer's disease is aging. Therefore, the increase in the number of patients associated with the aging population is particularly remarkable in Japan, the United States, and European countries, which are aging societies. I have. The number of Alzheimer's disease patients in Japan is estimated to be about 1 million, and it is expected that the number of Alzheimer's disease patients will increase as the population ages in the future. The cost of Alzheimer's disease patients, including nursing care costs, is thought to exceed 2.5 million yen per patient per year, so Japan has already paid socio-economic costs of more than 2.5 trillion yen. Become. It is now common knowledge in the world that treating Alzheimer's disease before or as soon as dementia manifests can have significant medical and economic benefits. However, at present, it is extremely difficult to accurately diagnose these stages of Alzheimer's disease.

[0003] There are various methods for diagnosing Alzheimer's disease at present. In Japan, Hasegawa formula, ADAS, MMSE
In general, a method for quantitatively evaluating a decrease in cognitive function of an individual suspected of having Alzheimer's disease is used, and an imaging diagnostic method (MRI, CT, or the like) is rarely used as an auxiliary method.
However, these diagnostic methods are not sufficient to confirm the disease, and a definitive diagnosis requires a biopsy of the brain before living (biopsy) and a histopathological examination of the postmortem brain. Thus, despite the vigorous research on diagnostic methods for Alzheimer's disease, little progress has been made. Many studies have shown that Alzheimer's characteristic neurodegeneration has already begun long before the first clinical symptoms appear (about 40 years in the longest). It is also known that when the family or clinician surrounding the patient notices the first clinical symptoms of the disease, the brain pathology has already progressed to an irreversible state. In view of the progression characteristics of the above-mentioned disease states and the rapid increase in the number of patients, the necessity and significance of accurate early diagnosis of Alzheimer's disease are extremely large.

[0004] The pathological image of Alzheimer's disease is represented by two main features. Senile plaques and neurofibrillary tangles. The main component of the former is amyloid β protein having a β sheet structure, and the latter is hyperphosphorylated tau protein. Definitive diagnosis of Alzheimer's disease relies on the appearance of these pathological features in the patient's brain. The significance of amyloid β protein in the pathogenesis of Alzheimer's disease is known as follows (Katsuhiko Yanagisawa, Yasuo Ihara: Advances in Neurological Research, Vol. 41,
70-79, 1997, Mikio Tokaibayashi: Dementia Japan, Vol. 11, pages 43-50, 1997
Akira Tamaoka: Dementia Japan, Vol. 11, 51-
57, 1997). 1. Diffuse deposition of amyloid β protein (Aβ) is considered to be the earliest neuropathological change in Alzheimer's disease brain. 2. Aβ precursor amyloid precursor protein (AP
P) Presence of familial Alzheimer's disease with a point mutation in the gene. 3. Abnormal production of Aβ in cultured cells into which the gene of 2. has been introduced. 4. Abnormal production of Aβ is also observed in presenilin gene abnormalities, which account for the majority of familial Alzheimer's disease. 5. A neuropathological change similar to Alzheimer's disease brain appears early in the brain of a group of Down syndrome having trisomy of chromosome 21 in which the gene encoding APP exists. As described above, the amyloid β protein is characteristic of a disease in which amyloid is accumulated, including Alzheimer's disease, and is closely related. Therefore, detection of an amyloid β protein having a β sheet structure as a marker in the body, particularly in the brain, is one of important diagnostic methods for diseases in which amyloid accumulates, particularly Alzheimer's disease.

For the purpose of diagnosing amyloid accumulation diseases such as Alzheimer's disease, a substance that specifically binds to and stains amyloid β protein in the body, especially in the brain, has been conventionally searched. Such substances include Congo Red (Puchtler et al., Journal of Histochemistry and Cytology, Vol. 77, p. 431, 1983) and Thioflavin S (Puchtler et al., Journal of Histochemistry and cytochemistry, Vol. 10, p. 35, 1962), Thioflavin T (LeVine, Protein Science, Vol. 2, pp. 404-410, 1993) and chrysamine G and its derivatives (international patents). Application PCT
/ US96 / 05918, PCTUS98 / 0588
9) and the like are reported, but no report is made for compounds in other groups. The reported compounds have many problems in terms of binding specificity to amyloid β protein, blood-brain barrier permeability, solubility, toxicity and the like.
Therefore, at present, these reported compounds have not yet been put to practical use in the diagnosis of diseases in which amyloid accumulates.

[0006]

SUMMARY OF THE INVENTION In view of the above circumstances, the present invention relates to a substance which has high binding specificity to β-amyloid protein and high blood-brain barrier permeability and can be used as a diagnostic probe for a disease in which amyloid is accumulated. Thus, it provides a different group of substances from conventional substances. The present invention also provides such a labeled substance used as an imaging diagnostic probe for a disease in which amyloid accumulates, and a diagnostic imaging composition containing such a probe.

[0007]

Means for Solving the Problems and Embodiments of the Invention
The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, have found that Basic Blue 41 and palatin fast black, or a salt or solvate thereof, have a very high binding specificity to β-amyloid protein, In addition, they have found that they have blood-brain barrier permeability, and have completed the present invention.

That is, the present invention relates to (1) Basic
Blue 41 and Palatin Fast Black WAN
A compound for imaging diagnostic probe of a disease in which amyloid accumulates, or a salt or solvate thereof, (2) a labeled compound of (1) or a salt or solvate thereof, selected from the group consisting of: A) a compound or a salt or solvate thereof according to (1), which is labeled with a radionuclide; and (4) a compound which is labeled with a positron-emitting nuclide selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F. Amyloid containing the compound according to (1) or a salt or solvate thereof, and (5) the compound according to (1) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier. A composition for diagnostic imaging of disease, (6) a composition according to (5), wherein the compound is labeled, (7) a composition according to (5), wherein the compound is labeled with a radionuclide, and (8) a compound according to (5). ¹¹ C, ¹³ N ¹⁵ O, ¹⁸ positron emission being labeled with (5) selected from the group consisting of F composition according,
(9) A kit for image diagnosis of a disease in which amyloid accumulates, comprising the compound according to (1) or a pharmaceutically acceptable salt or solvate thereof as an essential component, and (10) the compound is labeled ( The kit according to 9), the kit according to (9), wherein the compound is labeled with a radionuclide, and the positron wherein the compound is selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F. The kit according to (9), wherein the kit is labeled with a released nuclide. Is provided.

The substance used as an imaging diagnostic probe for a disease in which amyloid accumulates according to the present invention is a compound selected from the group consisting of Basic Blue 41 and Palatin Fast Black WAN, or a salt or solvate thereof. . Basic Blue 41 is:

Embedded image It is a compound shown by these. An onium ion is formed at the thiazole ring at the nitrogen, and a halide ion,
An onium salt may be formed with an anion such as a sulfonic acid ion or an organic acid ion such as CH ₃ SO ₃ ^— . Such salts are included in the present invention. Basic Blue 41 may also form solvates such as hydrates, methanol solvates, ethanol solvates, and ammonia solvates, and such solvates are also included in the present invention. Basic Blue 41
When used in the composition or kit of the present invention, its salt or solvate is preferably pharmaceutically acceptable. The pharmaceutically acceptable salts include, for example, onium salts with halide ions such as chlorine, bromine and iodine. Examples of the pharmaceutically acceptable solvates include hydrates, ethanol solvates and the like.

The palatin fast black WAN is represented by the following formula:

Embedded image It is a compound shown by these. The sulfonic acid groups in Palatin Fast Black WAN may form salts with metals such as alkali metals such as lithium, sodium and potassium, and alkaline earth metals such as magnesium, calcium and barium. Such salts are included in the present invention. Also, Palatin Fast Black WAN can form complexes with metals such as chromium, iron, and cobalt.
Such complexes are also included in the present invention. In the present invention, such a complex is included in the salt. Also, Palatin Fast Black WAN may form solvates such as hydrates, methanol solvates, ethanol solvates, and ammonia solvates, and such solvates are also included in the present invention. When palatin fast black WAN is used in the composition or kit of the present invention, the salt or solvate thereof is preferably pharmaceutically acceptable. Examples of the pharmaceutically acceptable salts include salts with sodium, potassium, calcium and the like, and complexes with iron, cobalt and the like. The pharmaceutically acceptable solvates include hydrates,
Ethanol solvates and the like.

In the present invention, Basic Blue 41 and Palatin Fast Black WA specifically bind in vivo to amyloid in the body in a disease in which amyloid accumulates, specifically β-amyloid protein.
A compound selected from the group consisting of N or a salt or solvate thereof is used as a diagnostic probe for a disease in which amyloid is accumulated. As used herein, the term "amyloid-accumulating disease" refers to a disease characterized by deposition of amyloid protein, specifically β-amyloid protein in the body as described above, which can be diagnosed using this as a marker, such as Alzheimer's disease and Down's syndrome. And the like.

In diagnosing a disease in which amyloid accumulates, it is common to use a labeled product of the compound of the present invention as a probe. Labels include fluorescent substances, affinity substances, enzyme substrates, radionuclides, and the like. For imaging diagnosis of a disease in which amyloid is accumulated, a probe labeled with a radionuclide is usually used. The compounds of the present invention can be labeled with various radionuclides by methods well known in the art. For example, ³ H, ¹⁴ C, ³⁵ S, ¹³¹ I, etc. are radionuclides that have been used before, and are often used in vitro. The general requirements for an imaging diagnostic probe and its detection means are that it can be diagnosed in vivo, that it is less harmful to the patient (especially that it is non-invasive), that it has high detection sensitivity, and that it has an appropriate half-life. (Appropriate label probe preparation time and diagnostic time). Therefore, recently, positron emission tomography (PET) using gamma rays showing high detection sensitivity and material permeability or computed tomography using single photon emitting nuclides (SPECT) has come to be used. Among them, PET is preferable because two γ-rays emitted from positron-emitting nuclides in opposite directions are detected by a coincidence method using a pair of detectors, so that information excellent in resolving power and quantitativeness can be obtained. . For SPECT
^99m Tc, ¹¹¹ In, ⁶⁷ Ga, ²⁰¹ Tl, ¹²³ I, ¹³³ Xe
The compounds of the present invention can be labeled with single photon emitting nuclides such as For PET, ¹¹ C, ¹³ N, ¹⁵ O, ¹⁸ F, ⁶² Cu,
^The compound of the present invention can be labeled with a positron emitting nuclide such as ⁶⁸ Ga, ⁷⁶ Br. Among positron emitting nuclides, ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F are preferable because the half-life is appropriate. Generally, these nuclides are produced by equipment called cyclotrons or generators.
Those skilled in the art can select a production method and an apparatus according to the produced nuclide. The nuclide thus produced can be used to label the compound of the present invention.

[0013] Methods for producing labeled compounds labeled with these radionuclides are well known in the art. Representative methods include chemical synthesis, isotope exchange, and biosynthesis. Chemical synthesis methods have been widely used in the past, and are essentially the same as ordinary chemical synthesis methods except for using radioactive starting materials. Various nuclides are introduced into the compound by this method. The isotope exchange method is a method in which ³ H, ³⁵ S, ¹²⁵ I, etc. in a compound having a simple structure are transferred into a compound having a complicated structure to obtain a compound having a complex structure labeled with these nuclides. . The biosynthesis method is a method in which a compound labeled with ¹⁴ C, ³⁵ S or the like is given to cells such as microorganisms to obtain a metabolite into which these nuclides have been introduced. Regarding the label position, a label can be introduced at a desired position by designing a synthesis scheme according to the purpose in the same manner as in ordinary synthesis. Such designs are well-known to those skilled in the art. Also, for example, ¹¹ C, ¹³ N, ¹⁵ O, ¹⁸
When a positron emitting nuclide such as F is used, a desired nuclide is obtained from a (ultra) small cyclotron installed in a facility such as a hospital, and a desired compound is labeled at a desired position by the above-described method, and is immediately diagnosed and tested. It can also be used for medical treatment. The desired nuclide can be introduced and labeled at a desired position of the compound of the present invention by these methods known to those skilled in the art.

The administration of the labeled compound of the present invention to a subject may be local or systemic. The administration route includes intradermal, intraperitoneal, intravenous, arterial, or spinal fluid injection or infusion, etc., which can be selected according to factors such as the type of disease, nuclide used, compound used, target condition, and test site. . After the probe of the present invention has been administered and a sufficient time has passed for binding and disintegration to β-amyloid protein, P
The inspection site can be examined by means such as ET and SPECT. These means can be appropriately selected depending on factors such as the type of disease, nuclide used, compound used, condition of the subject, and test site. The dose of the compound of the present invention labeled with a radionuclide depends on the type of disease, nuclide used, compound used, age of the subject,
It varies depending on the physical condition, gender, degree of disease, site to be examined, and the like. In particular, it is necessary to pay close attention to the exposure dose of the target. For example, the radioactivity of the compound of the present invention labeled with a positron-emitting nuclide such as ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F is usually 3.7 to 3.7 gigabecquerel, preferably 18 megabecquerel to 740
It is in the mega becquerel range.

The present invention also relates to an amylo containing the compound of the present invention.
Provided is a composition for diagnostic imaging of a disease in which id accumulates. Book
The invention composition comprises the compound of the invention and a pharmaceutically acceptable carrier.
Including the body. The compound of the present invention in the composition must be labeled.
Is preferred. There are various labeling methods as described above.
Radionuclides (especially for¹¹C, ¹³
N,¹⁵O,¹⁸Labeled with a positron emitting nuclide such as F)
Is desirable. The form of the composition of the present invention depends on its purpose.
It is preferable to be in a form that allows injection or infusion.
Good. Therefore, a pharmaceutically acceptable carrier is a liquid.
Are preferred, potassium phosphate buffer, physiological saline
Aqueous solvents such as water, Ringer's solution, distilled water, etc., or
Polyethylene glycol, vegetable fats, ethanol,
Lyserine, dimethyl sulfoxide, propylene glyco
Non-aqueous solvents such as but not limited to
No. The compounding ratio of the carrier and the compound of the present invention depends on the site of application,
It can be selected as appropriate depending on the delivery method, etc.
1 to 2 to 1 ratio, preferably not 10,000 to 1
And a ratio of 10: 1. Further, the composition of the present invention further comprises
Known antibacterial agents (eg, antibiotics), local anesthetics (eg,
For example, procaine hydrochloride, dibucaine hydrochloride, etc.), buffer
(For example, Tris-HCl buffer, Hepes buffer
Osmotic agents (eg, glucose, sorbitol)
, Sodium chloride, etc.).

The present invention further provides a kit for diagnostic imaging of a disease in which amyloid accumulates, comprising the compound of the present invention as an essential component. Usually, the kit comprises a compound of the present invention, a solvent for dissolving the compound, a buffer, an osmotic pressure regulator,
Each component such as an antibacterial agent and a local anesthetic is separately or several together put in each container. The compound of the present invention may be unlabeled or labeled. When unlabeled, the compounds of the present invention can be labeled before use by conventional methods as described above. The compound of the present invention may be provided as a solid such as a lyophilized powder, or may be provided after being dissolved in an appropriate solvent. The solvent may be the same as the carrier used in the composition of the present invention described above. Also,
Each component such as a buffer, an osmotic pressure regulator, an antibacterial agent, and a local anesthetic may be the same as that used in the above-mentioned composition of the present invention. Various containers can be appropriately selected,
It can be formed into a shape suitable for label introduction operation to the compound of the present invention, it may be made of a light-shielding material depending on the properties of the compound, or a vial or a syringe or the like for convenient administration to patients. It can also be shaped. Also,
The kit may appropriately include instruments necessary for diagnosis, for example, instruments used for a syringe, an infusion set, or a PET device. Usually, instructions are attached to the kit.

Furthermore, since the compound of the present invention specifically binds to the amyloid β protein, the compound of the present invention can be used in the form of unlabeled or unlabeled amyloid β protein in vitro.
It can also be used for protein detection, quantification, and the like. For example,
The compound of the present invention may be used for amyloid β protein staining of a microscope specimen, colorimetric determination of amyloid β protein in a sample, or determination of amyloid β protein using a scintillation cowinter.

Next, a method for screening the compound of the present invention will be described. (1) Method for quantifying amyloid β protein having β-sheet structure-method for measuring recognition degree of β-structure of test compound Several methods for quantifying amyloid β protein having β-sheet structure in vitro have already been reported. However, in the present invention, the method of LeVine (protein science, 2
Vol., Pp. 404-410, 1993) and the method of Woods et al. (Journal of Molecular Biology, 256, 870-877, 1996). That is, amyloid β protein (purchased from Peptide Research Laboratories) was dissolved in potassium phosphate buffer (pH 7.4) and left at 37 ° C. for 4 days. A test compound (final concentration: 1 micromolar) dissolved in the same buffer was dispensed in 50 microliter portions into a 96-well microplate, and then amyloid β was allowed to stand for 4 days.
The protein solution was added in 50 microliter increments. Then, 100 μl of Thioflavin T (which emits fluorescence depending on the degree of β structure of amyloid β protein) dissolved in a glycine-NaOH buffer (pH 8.5) was added in 100 μl portions (final concentration: 3 μM), and the fluorescence was immediately measured. Microplate reader (Molecular Device, fmax
(Type), the fluorescence was measured at an excitation wavelength of 442 nanometers and a measurement wavelength of 485 nanometers. Assuming that the fluorescence intensity of thioflavin alone is A, that in the coexistence of amyloid β protein and thioflavin T is B, and that in the coexistence of amyloid β protein, thioflavin T and the test compound is C, the β structure recognition degree of each test compound is as follows: It was calculated by the formula (unless otherwise specified, the test compound concentration was 1 micromolar). Test compound β structure recognition degree (%) = ｛(BC) / (B−
A) ΔX100 It can be said that the higher the β structure recognition degree, the higher the binding specificity of the test compound to the amyloid β protein.

(2) Method of Measuring Partition Coefficient of Test Compound It is known that the partition coefficient of a compound between water and lipid is an index of the blood-brain barrier permeability of the compound (Begley, Journal of Pharmacy)・ And Pharmacology Vol. 48, pp. 136-146, 1996
Year, and Butchwald and Boulder, Current Medicinal Chemistry, 5, 353-380, 1998). Therefore, the water / 1-octanol partition coefficient was measured to be an index of blood-brain barrier permeability. 1-octanol was used for the oil phase, and a phosphate buffer (pH 7.3) or ultrapure water was used for the aqueous phase. An appropriate amount of the test compound was dissolved in an oil phase or an aqueous phase, and both phases were placed in the same test tube and shaken vigorously at room temperature for 30 minutes. After leaving still at room temperature for 1 hour or more, it was centrifuged at 2,000 rpm for 10 minutes and left still at room temperature for 1 hour. The aqueous phase and the oil phase were each sampled and transferred to a 96-well microplate. Using a microplate reader (Molecular Devices, Spectramax 250)
The absorbance was measured at the maximum absorption wavelength of each test compound, and the concentration of the test compound was calculated from a calibration curve obtained in advance. The distribution coefficient was calculated by the following equation. Partition coefficient of test compound = concentration of test compound in oil phase / concentration of test compound in water-oil phase The larger this partition coefficient, the higher the blood-brain barrier permeability of the test compound.

(3) Calculation of useful coefficient The useful coefficient is defined as the product of the β structure recognition degree (specificity of the test compound binding to the amyloid β protein) and the partition coefficient (the blood-brain barrier permeability of the test compound). Then, this coefficient is considered to be an index of how much the test compound binds to amyloid β protein in the brain when the test compound is actually administered to humans. The useful coefficient of each test compound was calculated by the following equation. Usefulness coefficient of test compound = β structure recognition degree of test compound ×
Partition Coefficient of Test Compound The larger the useful coefficient, the more suitable the test compound is as a diagnostic probe for a disease in which amyloid accumulates.

[0021]

EXAMPLES The present invention will be specifically described below with reference to examples, but these examples do not limit the present invention in any way. Β of the compound of the present invention obtained by the above measurement method
Table I shows the values of the structure recognition degree, the distribution coefficient, and the useful coefficient. As a comparative example, compounds (congo red and chrysamine G) which are conventionally known to bind to amyloid β protein
Table I also shows the measurement results under the same conditions for
The structural formula in Table I shows an example of the existence form of the compound. The measured values are the average of two experiments.

[Table 1] Table I As shown in Table I, it can be seen that Basic Blue 41 and Palatin Fast Black WAN, which belong to a different group from the conventionally reported compounds, recognize the β structure and can penetrate the blood-brain barrier. Basic Blue 41 is more beta than Congo Red and Chrysamine G
Structure recognition was high. The palatin fast black WAN also had higher β structure recognition than chrysamine G. In addition, all of the tested compounds of the present invention had higher partition coefficients than Congo Red. Basic Blue 4
The useful coefficient of 1 was similar to that of chrysamine G, and that of palatin fast black WAN was larger than that of Congo red. Therefore, these compounds of the present invention can specifically bind to amyloid β protein, have relatively high blood-brain barrier permeability, and can be said to be highly useful as diagnostic probes for diseases in which amyloid is accumulated.

[0022]

As described above, according to the present invention,
Amyloid β belongs to a different group from conventional compounds.
Disclosed are a compound for imaging diagnosis of a disease in which amyloid accumulates, which has a high binding specificity to a protein and a high blood-brain barrier permeability, and a composition and a kit for imaging a disease in which amyloid accumulates, including the compound. Use of such compounds, compositions, or kits allows for early and accurate diagnosis of disease.

Claims (12)

[Claims] 1. A compound for imaging diagnostic probe for a disease in which amyloid is accumulated, or a salt or solvate thereof, selected from the group consisting of Basic Blue 41 and Palatin Fast Black WAN. 2. The compound according to claim 1, which is labeled, or a salt or solvate thereof. 3. The compound according to claim 1, which is labeled with a radionuclide, or a salt or solvate thereof. 4. The compound according to claim 1, which is labeled with a positron-emitting nuclide selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F, or a salt or solvate thereof. 5. A composition for diagnostic imaging of a disease in which amyloid is accumulated, comprising the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier. 6. The composition according to claim 5, wherein the compound is labeled. 7. The composition according to claim 5, wherein the compound is labeled with a radionuclide. 8. The composition according to claim 5, wherein the compound is labeled with a positron emitting nuclide selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F. 9. A kit for diagnostic imaging of a disease in which amyloid accumulates, comprising the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof as an essential component. 10. The kit according to claim 9, wherein the compound is labeled. 11. The kit according to claim 9, wherein the compound is labeled with a radionuclide. 12. The kit according to claim 9, wherein the compound is labeled with a positron-emitting nuclide selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F.