How to obtain biometric information

Abstract

A biological information acquisition method according to the present invention has: a step for acquiring first information pertaining to the distribution of a first substance in a living organism or a portion of the living organism; a step for acquiring second information pertaining to the distribution of a second substance in a region of interest in the living organism or a portion of the living organism; and a step for acquiring third information, which pertains to the action / effect of the first substance or the second substance, on the basis of the first information and the second information.

Description

[Technical Field]

[0001] The present invention relates to a method for acquiring biometric information. [Background technology]

[0002] From candidate compounds for drugs, only those evaluated as effective are selected through screening. Drugs often bind to target substances such as receptors, enzymes, ion channels, and transporters in the body. After reaching cells and binding to the target substance, the drug exerts its efficacy by acting on the cells. Therefore, determining whether the drug has reached the target substance and whether the drug exerts its efficacy after reaching the target substance are important criteria in screening.

[0003] Known methods for investigating the efficacy of anticancer drugs and the like mainly involve measuring tumor size through nuclear medicine testing. Examples of imaging methods for measuring tumor size include positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI). Immunohistochemistry (IHC) is also used as a method for investigating the localization of drugs in tissues after drug administration (see, for example, Patent Documents 1 and 2). Furthermore, methods using fluorescent nanoparticles or phosphor-accumulated particles are known as methods for detecting the presence of specific substances (such as the aforementioned target substances) in vivo.

[0004] Patent Document 1 describes a method for detecting the distribution of a predetermined substance in a living body. In the method of Patent Document 1, a specific probe compound and a radioactive substance are administered to a living body, and after a predetermined time has passed, an image is taken using a PET device. Then, the distribution of the predetermined substance in the living body is detected from the acquired image.

[0005] Patent Document 2 describes a method for detecting specific substances in vivo using immunohistochemical staining. In the method described in Patent Document 2, breast cancer tissue cells are collected from a breast cancer patient, and breast cancer-related proteins in the collected specimen are labeled with fluorescent nanoparticles. Images of the labeled breast cancer-related proteins are used to predict pathological complete response to neoadjuvant breast cancer therapy. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] US Patent Application Publication No. 2019 / 0192697 [Patent Document 2] Japanese Patent Application Publication No. 2018-084568 Summary of the Invention [Problem to be solved by the invention]

[0007] However, as mentioned above, Patent Document 1 can grasp the general distribution of a drug in the body, but it is difficult to determine whether the drug actually reaches target cells or target proteins, and it cannot determine whether the drug is exerting its therapeutic effect on target cells. On the other hand, Patent Document 2 may be able to determine whether the drug is exerting its therapeutic effect by detecting substances related to the drug's action in collected tissue cells, but it is impossible to determine which part of the body to collect cell tissue from unless the distribution of the drug in the body, such as which part of the body the drug has reached, can be grasped. Furthermore, to grasp the general distribution of a drug in the body using the method of Patent Document 2, tissue cells must be collected from multiple parts of the body (e.g., multiple organs). This is unrealistic because it requires a huge amount of labor and places a heavy burden on experimental animals and test subjects. Thus, conventional methods have had difficulty in simultaneously confirming the presence of a drug (e.g., distribution in the body) and evaluating the drug's action (e.g., confirming whether the drug has a medicinal effect or whether its mechanism of action is exerted).

[0008] An object of the present invention is to provide a method for acquiring biological information that can simultaneously confirm the presence of a drug and evaluate the drug's effects. [Means for solving the problem]

[0009] A method for acquiring biological information as one means for solving the above problem includes the steps of acquiring first information regarding the distribution of a first substance in a living organism or a part of a living organism, acquiring second information regarding the distribution of a second substance in a region of interest within the living organism or the part of the living organism, and acquiring third information regarding the action effect of either the first substance or the second substance based on the first information and the second information. [Effects of the Invention]

[0010] According to the present invention, it is possible to simultaneously confirm the presence of a drug and evaluate the action of the drug. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a flowchart illustrating a method for acquiring biometric information according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0012] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A method for acquiring biometric information according to an embodiment of the present invention will be described in detail below with reference to the accompanying drawings.

[0013] FIG. 1 is a flowchart illustrating a method for acquiring biometric information according to an embodiment of the present invention.

[0014] As shown in Figure 1, a method for acquiring biological information according to one embodiment of the present invention includes a step (S110) of acquiring first information regarding the distribution of a first substance in a living organism or a part of a living organism, a step (S120) of acquiring second information regarding the distribution of a second substance in a region of interest in the living organism or part of the living organism, and a step (S130) of acquiring third information regarding the action effect of either the first substance or the second substance based on the first information and the second information.

[0015] In the step (S110) of obtaining first information, the first substance is labeled with a radioactive or magnetic substance, and first information regarding the distribution of the first substance in a living organism or a part of a living organism is obtained. For example, in the step (S110) of obtaining first information, a medical tomography device is used to image the first substance labeled with a radioactive or magnetic substance, and an image showing the distribution of the first substance in the living organism or a part of the living organism is obtained as the first information. Alternatively, a dedicated device equipped with a monochrome camera may be used to perform tomography of the first substance labeled with a fluorescent dye or fluorescent protein, etc., and the images may be processed and reconstructed to obtain, as the first information, an image showing the distribution of the first substance in 3D throughout the living organism.

[0016] The medical tomography device is not particularly limited as long as it can acquire first information regarding the distribution of the first substance. The medical tomography device is, for example, an X-ray CT device, an MRI device, or a PET device. When a CT device or a PET device is used, the first substance is labeled with a radioactive material, and when an MRI device is used, the first substance is labeled with a magnetic material.

[0017] The object from which the first information is acquired may be the entire living body (whole body), or a part of the living body such as the upper body, the lower body, or the periphery of a specific organ.

[0018] Examples of the first substance include drugs such as antibodies, antibody-drug conjugates (ADCs), and conventional pharmaceutical compounds, substances on which drugs act (target substances), or substances produced by the action of drugs (drug efficacy markers). Drugs include substances that inhibit DNA replication in cells. Examples of drugs include therapeutic drugs for various diseases, particularly anticancer drugs. The first substance may be of one type or of multiple types. Examples of the first substance also include cell markers such as substances that are specifically expressed in target cells on which the drug acts (e.g., cancer cells or immune cells), substances that are specifically expressed in cells other than the target cells involved in the action of the drug, and substances that are specifically expressed in other cells present in the vicinity of the target cells.

[0019] Examples of the first information include the tissues to which the first substance has migrated, the extent to which the first substance has accumulated, and the extent to which the first substance has spread. The number of times the first information is acquired is not particularly limited. The first information may be acquired once or multiple times. For example, when the first substance is a drug, the timing of acquiring the first information when acquired once is preferably after administration of the first substance. When acquiring the first information multiple times, the timing of acquiring the first information may be once before administration of the first substance and once after administration of the drug, or multiple times after administration of the first substance. Specifically, the distribution of the drug before and after administration of the drug to a living body can be acquired as the first information. Furthermore, by acquiring the first information multiple times and comparing the results, information on the changes in the first substance over time can be obtained.

[0020] For example, when obtaining first information from an image captured by a PET device, an antibody or a drug that specifically binds to a target substance (e.g., cancer cells) is modified with a radioactive substance such as a radioisotope and administered to a subject (living body) such as a human or animal. Examples of radioisotopes include: 64 Cu, 124 I, 89Zr is included. After a predetermined time has passed since administration, the subject is photographed using a PET device to obtain images. The radioisotope used and the time from administration of the drug to obtaining images using the PET device are appropriately determined depending on the half-life of the radioisotope used and the purpose of the observation or examination.

[0021] The amount of the first substance may be further calculated from the acquired image. For example, a first region of interest (e.g., a region corresponding to an organ where the target substance is present) containing the drug (first substance) may be set, and the amount of drug in the first region of interest may be calculated from the intensity of the corresponding radiation signal. For example, a calibration curve may be used to convert the signal intensity into the amount (weight) of the drug. The first region of interest may be directly specified by the user or extracted from an image acquired by a PET device through image processing. When setting the first region of interest, an image acquired by an X-ray CT device of the subject may also be referenced. When an image acquired by an X-ray CT device of the subject is further referenced, the tumor area can be calculated by combining the radioisotope signal based on the image acquired by the PET device with the image acquired by the X-ray CT device. The amount of drug (first substance) may be the amount of radiation signal itself without being converted to an actual amount, or may be the amount per unit area rather than the total amount in the region of interest. When images of the subject taken by an X-ray CT scanner are further referenced, the tumor area can be calculated from the images taken by the PET scanner and the images taken by the X-ray CT scanner, so that an increase or decrease in the tumor area can be detected by acquiring the first information multiple times. Note that the first region of interest can also be set in the images obtained by the X-ray CT scanner and the MRI scanner in a similar manner, and the amount of medicine and the tumor area can be calculated.

[0022] When a drug effect marker or a cell marker is used as the first substance, for example, a tumor region is set as the first region of interest.

[0023] In the step of acquiring second information (S120), second information relating to the distribution of a second substance in a second region of interest in the living body or a part of the living body is acquired.

[0024] The second region of interest is preferably determined based on the first information. For example, the second region of interest from which the second information is obtained is identified based on a location where the first substance is most highly accumulated (e.g., a region with the highest amount of medicine: first information) or a location where the first substance is least highly accumulated (e.g., a region with the lowest amount of medicine: first information).

[0025] Examples of the second substance are the same as the examples of the first substance, but the first substance and the second substance are not the same substance. That is, for example, if the first substance is a drug, the second substance is a substance involved in the action of the drug (e.g., a substance on which the drug acts, a substance produced by the action of the drug, etc.). Also, if the first substance is a substance on which the drug acts or a substance produced by the action of the drug, the second substance is a drug.

[0026] The second information can be observed by labeling with, for example, a fluorescent substance. Examples of methods for labeling with a fluorescent substance and observing include immunohistochemical staining with fluorescent nanoparticles (HSTT; High Sensitive Tissue Testing). In the immunohistochemical staining with fluorescent nanoparticles method, for example, a section taken from the second region of interest is immunostained after a certain period of time has elapsed since administration of a drug, and an immunostained image is obtained in which the second substance is visualized by the fluorescent label.

[0027] Fluorescent nanoparticles can also be used as fluorescent labels. Phosphor-aggregated particles are nano-sized particles that have a structure in which multiple fluorophores (e.g., fluorescent dyes or semiconductor nanoparticles) are encapsulated within and / or adsorbed to their surfaces, based on an organic or inorganic particle. Examples of fluorescent dyes that make up fluorescent nanoparticles include rhodamine dyes, Cy dyes, Alexa Fluor® dyes, BODIPY dyes, squarylium dyes, cyanine dyes, aromatic ring dyes, oxazine dyes, carbopyronine dyes, and pyrromethene dyes. Examples of semiconductor nanoparticle materials that make up phosphor-aggregated nanoparticles include II-VI semiconductors, III-V semiconductors, or IV semiconductors. Phosphor-aggregated particles can be prepared according to known methods.

[0028] A recognition substance for specifically binding to a second substance is added to the phosphor-accumulated particle. The recognition substance is selected so that the phosphor-accumulated particle and the second substance bind directly or indirectly. Examples of recognition substances include proteins such as nucleotide chains, avidin, streptavidin, and antibodies, and low-molecular-weight compounds such as biotin. When the phosphor-accumulated particle and the first substance bind directly, an antibody that specifically binds to the first substance (primary antibody) can be used as the recognition substance. On the other hand, when the phosphor-accumulated particle and the second substance bind indirectly, an antibody (secondary antibody) that specifically binds to the antibody that specifically binds to the second substance (primary antibody) can be used as the recognition substance, or a substance that specifically binds to the primary antibody can be used.

[0029] In the immunostained image obtained by HSTT, the second substance labeled with a fluorescent substance appears as fluorescent bright spots. The number of bright spots in the HSTT image correlates with the amount of the second substance in the measured area. The amount of the second substance can be calculated from the number of bright spots in the HSTT image.

[0030] The second information is information regarding the distribution of the second substance in the second region of interest. If the first substance is a drug, the second information is the distribution of a target substance, a drug efficacy marker, a cell marker, or the like in the second region of interest. This makes it possible to detect the presence or amount of the second substance in the second region of interest, thereby confirming the presence or absence of drug action and its mechanism of action. Furthermore, if the first substance is a target substance, a drug efficacy marker, a cell marker, or the like, the second information is the distribution of the drug in the second region of interest. This makes it possible to determine whether the drug has reached the second region of interest.

[0031] In the step (S130) of obtaining third information, third information relating to the action and effect of either the first substance or the second substance is obtained based on the first information and the second information.

[0032] Examples of the third information include whether the drug is effective, whether there are side effects, and the dosage of the drug required to exert its effect.

[0033] The patterns for obtaining the third information are shown below. (1) As first information, the presence of a drug is detected by detecting a drug-derived signal in a first region of interest from an image captured by a medical tomography device. As second information, a drug efficacy marker, for example, is detected in a second region of interest from an image labeled with a fluorescent substance. If the drug has reached the first region of interest (first information) and the drug efficacy marker is detected in the second region of interest (second information), it is determined that the drug is effective because the drug has the action and effect of the drug that has reached it (third information).

[0034] (2) As first information, images taken before and after drug administration are acquired using a medical tomography device. Furthermore, based on the acquired images taken using a PET device before and after drug administration, it is determined whether the area of ​​the first region of interest has decreased before and after drug administration. As second information, the presence of a target substance, a pharmacological effect marker, or a cell marker in the second region of interest after drug administration is detected from the image labeled with a fluorescent substance. In this case, if the area of ​​the first region of interest has decreased before and after drug administration (first information) and the presence of a pharmacological effect marker is detected in the second region of interest after administration (second information), it is determined that the drug is effective (third information).

[0035] (3) As first information, the amount of drug in a first region of interest is obtained from an image captured by a medical tomography apparatus. As second information, the amount of target substance, pharmacological marker, or cell marker in a second region of interest is calculated from an image labeled with a fluorescent substance. The dosage can be determined or side effects can be predicted based on the amount of drug in the first region of interest (the amount of drug that has reached the first region of interest: accumulated amount) and the amount of drug whose medicinal action or mechanism of action has been confirmed, calculated from the amount of target substance, pharmacological marker, or cell marker in the second region of interest (effective amount). The dosage can be determined, for example, by calculating the ratio of the effective amount to the dosage (known), and by also referring to the minimum effective amount (known) necessary to exert a therapeutic effect, the minimum dosage necessary to exert a therapeutic effect can be calculated (third information). Furthermore, for example, in the step (S120) of acquiring second information, in addition to the second substance (target substance, drug efficacy marker, cell marker, etc.), the drug in the second region of interest may also be labeled with a labeling substance (e.g., a fluorescent substance with a different emission wavelength) different from the labeling substance that labels the second substance, and the amount of the drug in the second region of interest may be acquired. In this case, the effective amount can be calculated from the amount of the drug in the second region of interest, rather than from the amount of the second substance in the second region of interest, allowing for more accurate calculation of the dosage.

[0036] (4) As first information, the presence of a drug in a first region of interest is detected from an image captured by a medical tomography device. As second information, a target substance, a drug efficacy marker, or a cell marker in a second region of interest, and other drug efficacy markers or other cell markers in the second region of interest are detected from an image labeled with a fluorescent substance. The other drug efficacy markers or other cell markers are substances used to infer side effects. If a drug is detected in the first region of interest (first information) and a drug efficacy marker or a cell marker and other drug efficacy markers or other cell markers are detected in the second region of interest (second information), it can be assessed that there is a possibility of side effects occurring (third information).

[0037] (5) As first information, from an image captured by a medical tomography apparatus, a drug is also detected in other first regions of interest (e.g., other organs) that are not the first region of interest where the drug is originally intended to reach. As second information, from an image labeled with a fluorescent substance, a target substance, a pharmacological marker, or a cell marker is also detected in other second regions of interest determined based on the other first regions of interest. For example, if a drug is detected in the first region of interest and the other first regions of interest (first information), but a target substance is detected in the second region of interest while not detected in the other second regions of interest (second information), it can be assessed that a side effect may occur (third information).

[0038] In the examples (1) to (5), medicine may be further detected as the second information.

[0039] (6) In the examples of (1) to (5), a drug is detected as the first information, and a target substance, a drug efficacy marker, or a cell marker is detected as the second information, but a target substance, a drug efficacy marker, or a cell marker may be detected as the first information, and a drug may be detected as the second information. In this case, too, third information indicating the action and effect of the drug can be obtained.

[0040] (effect) As described above, according to the present invention, second information regarding the mechanism of action of a drug is obtained based on first information about a first substance, and third information regarding the drug's effects is obtained based on the first information and the second information, thereby enabling the drug's effects to be evaluated.

[0041] This application claims priority from Japanese Patent Application No. 2020-155789, filed September 16, 2020. The entire contents of the specification and drawings of that application are incorporated herein by reference. [Industrial Applicability]

[0042] The method for confirming the effect of a drug according to this embodiment is useful for, for example, screening drugs, proving the mechanism of action of drugs, and evaluating the toxicity of drugs.

Claims

1. obtaining first information regarding the distribution of a first substance in a living organism or a part of a living organism; obtaining second information about the distribution of a second substance in a region of interest of the organism or part of the organism; acquiring third information relating to an effect of either the first substance or the second substance based on the first information and the second information; and In the step of acquiring the first information and the step of acquiring the second information, one of the steps acquires the first information or the second information by labeling the first substance or the second substance with a radioactive substance or a magnetic substance, and the other acquires the first information or the second information by labeling the first substance or the second substance with a fluorescent substance. How to obtain biometric information.

2. The method for acquiring biological information according to claim 1 , wherein one of the first substance and the second substance is a medicine.

3. the first substance is the medicine administered to the living body, The second substance is a substance on which the drug acts or a substance produced by the action of the drug. The method for acquiring biometric information according to claim 2 .

4. the first substance is a substance on which the drug acts or a substance produced by the action of the drug, the second substance is the medicine administered to the living body; The method for acquiring biometric information according to claim 2 .

5. The method for acquiring biological information described in claim 3, wherein in the step of acquiring the first information, the distribution of the drug before the drug is administered to the living body and the distribution of the drug after the drug is administered to the living body are acquired as the first information.

6. 2. The method for acquiring biological information according to claim 1, wherein the step of acquiring the first information comprises using a medical tomography apparatus to acquire the first information by imaging the first substance labeled with the radioactive substance or magnetic substance.

7. The method for acquiring biological information according to claim 1 , wherein the step of acquiring the second information comprises acquiring the second information by photographing the second substance labeled with the fluorescent substance using a fluorescence microscope.

8. The method for acquiring biological information according to claim 6, wherein the medical tomography device is an X-ray CT device, an MRI device, or a PET device.

9. The method for acquiring biological information according to claim 1 , wherein the region of interest is determined based on the first information.

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