TWI816951B - Neutron diagnostic equipment - Google Patents

Abstract

A neutron diagnostic device, including a compound containing a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, a neutron generating part including a decelerator for decelerating neutrons, and a gamma detector for detecting gamma rays The radiation detection part, the neutron diagnostic device further includes: a neutron source, after the compound is injected into the living body as the observation object, the compound generates a predetermined relationship between the normal tissue and the diseased tissue in the injected living body. During the period of concentration difference in the tissue, the living body is irradiated with neutrons; and the output unit uses the gamma ray detection unit to observe the γ-ray detection unit emitted due to the reaction between the elements contained in the compound and the neutrons in the living body irradiated with the neutrons. The resulting output of gamma rays.

Description

neutron diagnostic device

The present invention relates to neutron diagnostic equipment.

This case claims priority based on U.S. Provisional Patent Application No. 62/777,776 filed in the United States on December 11, 2018, the content of which is incorporated herein by reference.

Positron emission tomography (PET) examination uses a diagnostic agent labeled with a radioactive isotope with a short half-life to detect gamma rays produced by nuclei that emit positrons. For example, when testing using a diagnostic agent using ¹⁸ F, the goal is to take the image within 120 minutes after adding the diagnostic agent. In fact, imaging takes about 30 to 40 minutes, so in most cases, the subject is kept still for about an hour after administering the diagnostic agent, and then the PET examination is performed (for example, see "Non-Patent Document 1").

Among the diagnostic agents used in PET examinations, radioactive isotopes with short half-lives are used. When a radioactive isotope with a long half-life is used, the subject continues to be exposed to the diagnostic agent until it is excreted from the body, and there is a concern that the amount of radiation exposure in the subject's body will increase.

Because of their short half-lives, diagnostic agents are synthesized just before the examination begins. Because diagnostic reagents are used that are synthesized just before the examination begins, the hospital must have equipment to synthesize the diagnostic reagents, or the diagnostic reagents must be transported from the manufacturing site to the hospital within approximately one hour.

[Prior technical literature]

[Non-patent literature]

[Non-patent document 1]

"FDG PET, PET/CT Diagnosis and Treatment Guidelines 2018", [online], Japanese Society of Nuclear Medicine, [retrieved on March 28, 2019], URL: http://jsnm.sakura.ne.jp/wp_jsnm/wp -content/uploads/2018/09/fdg_pet_petct_gl_2018_180918.pdf>

In PET examinations, when a diagnostic agent is labeled with a radioactive isotope with a short half-life, such as a diagnostic agent using ¹⁸ F, imaging must be performed within 120 minutes after the diagnostic agent is administered. Within 120 minutes after injection, the diagnostic agent may not be fully accumulated in the lesion and may be distributed in high concentrations to other parts.

Furthermore, when radioactive isotopes with short half-lives are used, the diagnostic agent must be synthesized just before the examination is started. In order to synthesize the diagnostic reagents immediately before the examination, the hospital must have a device for synthesizing the diagnostic reagents, or the diagnostic reagents must be transported from the manufacturer of the diagnostic reagents immediately before use.

In addition, diagnostic agents using radioactive isotopes with short half-lives cannot be stored for long periods of time, and therefore cannot be mass-produced to reduce costs.

Furthermore, the diagnostic agent itself becomes a gamma ray source, and in order to be administered into the body, it must be suppressed below a certain value. Furthermore, until the diagnostic agent is discharged from the body, it is necessary to avoid contact with pregnant women and infants, and to wash hands thoroughly after going to the toilet, etc., which imposes restrictions on daily life.

The present invention has been made in view of the above-mentioned points, and an object thereof is to provide a neutron diagnostic apparatus and a neutron diagnostic method that can provide flexibility in the time between the injection of a diagnostic agent and the imaging.

One aspect of the present invention is a neutron diagnostic device, which is a neutron diagnostic device including a compound composed of a stable element, a neutron generating part and a gamma ray detecting part; the stable element has a neutron capture cross-sectional area of Stable elements above 1000barn (1000×10 ^-28 m ² ); the neutron generating part has a decelerator to decelerate neutrons; the gamma ray detection part detects gamma rays; the neutron diagnostic device includes: a neutron source, After the compound is injected into the living body that is the object of observation, during the period when the compound generates a predetermined tissue concentration difference between the normal tissue and the diseased tissue in the living body to which the compound is injected, the living body is irradiated with neutrons; and the output unit , the gamma ray detection unit observes and outputs the result of gamma rays emitted due to the reaction of the elements contained in the compound with the neutrons in the living body that has been irradiated by the neutrons.

In the neutron diagnostic device according to one aspect of the present invention, the compound injected into the living body is a molecular target substance bonded to a specific molecule of the human being, and the bonded or contained neutron capture cross-sectional area is 1000 barn (1000 barn). ×10 ^-28 m ² ) or more, and the compound is absorbed or accumulated in the lesion of the living body.

In one aspect of the neutron diagnostic device of the present invention, the stable element containing the neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more contained in the compound is boron (B) or gallium (Gd). .

In one aspect of the neutron diagnostic apparatus of the present invention, the neutron source performs pulse irradiation with a neutron irradiation time of 0.1 seconds to 10 seconds.

In one aspect of the neutron diagnostic device of the present invention, the compound added to the living body contains a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, and the concentration is high The proportion of isotopes found in nature.

In one aspect of the neutron diagnostic device of the present invention, the neutron source is started when the compound containing the stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more is introduced into the living body. After more than 3 hours have elapsed, the neutrons are irradiated again.

In one aspect of the neutron diagnostic device of the present invention, the neutron source is located between the normal tissue and the diseased tissue in the injected living body after the compound is injected into the tissue of the compound. While the concentration difference is 1 to 2.0 or more, the neutrons are irradiated.

In one aspect of the neutron diagnostic device of the present invention, the compound injected into the living body is bound to or contains either or both of the glucose absorbed by the tumor tissue and the glucose accumulated in the tumor tissue. The neutron captures the stable element with a cross-sectional area above 1000barn (1000×10 ^-28 m ² ).

In one aspect of the neutron diagnostic device of the present invention, the compound injected into the living body has a boron-containing compound, and among the molecular target substances bonded to specific molecules of the human body, or glucose and glucose absorbed by the tumor tissue Either or both of the glucose accumulated in the tumor tissue are bound to or contain one or more boron-containing compounds.

One aspect of the present invention is a neutron diagnostic method, which includes a compound containing a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, and a decelerator for decelerating neutrons. The neutron diagnostic method is executed by a neutron diagnostic device with a neutron generating unit and a gamma-ray detecting unit that detects gamma rays; the neutron diagnostic method includes the following steps: after the compound is injected into the living body as the observation target, after the compound is injected into the injected body, The steps of irradiating the living body with neutrons during a period when a predetermined intra-tissue concentration difference occurs between the normal tissue and the diseased tissue in the living body; and observing the γ-ray detection part in the living body that has been irradiated with the neutrons because of the A step in which the elements contained in the compound react with the neutrons to emit gamma rays and output the result.

According to the embodiments of the present invention, it is possible to provide a neutron diagnostic apparatus and a neutron diagnostic method that can make the time from the injection of the diagnostic agent for PET examination to the time before imaging flexible.

100, 500: Neutron diagnostic device

101, 400-1~400-8: Neutron source

102: Reducer

103: Neutron Generation Department

200-1~200-6, 420-1~420-16: γ-ray camera

300:Analysis device

410-1~410-8: Reducer material

NB: Neutron

BT: brain tumor

PA:patient

IA: Boron-containing molecular target diagnostic agent

S1~S4: steps

[Fig. 1] is a schematic diagram showing an example of the neutron diagnostic device according to the first embodiment.

[Fig. 2] A diagram illustrating the boron neutron capture reaction.

[Fig. 3] is a diagram showing an example of the operation of the neutron diagnosis method.

[Fig. 4] is a diagram showing an example of an image obtained by a PET diagnostic apparatus.

[Fig. 5] is a diagram showing an example of an image obtained by the neutron diagnostic device according to this embodiment.

[Fig. 6A] is a schematic diagram showing an example of the neutron diagnostic device according to the second embodiment.

[Fig. 6B] is a schematic diagram showing an example of the neutron diagnostic device according to the second embodiment.

Next, the neutron diagnostic device and the neutron diagnostic method according to the embodiments will be described with reference to the drawings. The embodiment described below is only an example, and the embodiment to which the present invention is applied is not limited to the following embodiment.

In addition, in all the drawings used to explain the embodiments, those having the same functions are represented by the same symbols, and repeated descriptions are omitted.

In addition, the "based on XX" referred to in this case means "based on at least XX", and also includes cases where other requirements are based on other than XX. Also, "according to XX" is not limited to the direct use of XX. It also includes cases based on the results of calculation or processing of XX. "XX" is any requirement (for example, any information).

(First implementation mode)

(Neutron Diagnostic Device)

FIG. 1 is a schematic diagram showing an example of the neutron diagnostic device according to the first embodiment.

The neutron diagnostic apparatus 100 according to the first embodiment irradiates the patient with neutron NB. Before irradiating the patient with neutron NB, a compound composed of a stable element containing a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more is administered to the patient, and after the compound is administered to the patient, established time.

Among the compounds, among the molecular target substances bonded to human specific molecules such as human receptors, regulatory factors, antigens, etc., the bond either contains, or both bonds and contains a neutron capture cross-sectional area of 1000barn (1000× Stable elements above 10 ^-28 m ² ). Here, an example of the molecular target substance is a human chimeric antibody, a humanized antibody, or the like. Compounds are either or both absorbed into and accumulated in diseased parts such as tumors. As an example, a compound in which either or both of glucose absorbed by tumor tissue and glucose accumulated in tumor tissue is bonded, or is bonded and contains a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) and above stable elements.

The stable element contained in the compound may be bonded to, contain, or may be bonded to and contain a boron-containing compound such as BSH (Disodiummercaptoundecahydrododecaborate), carborane, or BPA (Borono-phenylalanine). That is, the compound has a boron-containing compound, among the molecular target substances bonded to human-specific molecules such as receptors, regulatory factors, antigens, etc. found in human tumor cells, or glucose and glucose absorbed by tumor tissues. One or both of the glucoses accumulated in the tumor tissue may be bonded with, or may be bonded with, a boron-containing compound. In the compound, A boron-containing compound is bonded to or contains a plurality of molecules at a high concentration of 1 or more molecules, or is bonded to and contains a boron-containing compound at the same time. Here, an example of a molecular target substance is a human chimeric antibody, a humanized antibody, or the like.

Furthermore, in the compound, the content ratio of stable elements with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more is higher than the concentration ratio of isotopes existing in nature.

The stable element contained in the compound with a neutron capture cross-sectional area above 1000barn (1000×10 ^-28 m ² ) is boron (B) or gallium (Gd).

In this embodiment, the following describes the use of a boron agent labeled with a specific substance using the stabilizing element boron ( ¹⁰ B) as a stabilizing element including a stabilizing element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more. An example of the compound formed.

The predetermined time is a period during which, after the compound is administered to the patient, a tissue concentration difference is generated between the normal tissue and the diseased tissue of the living body to which the compound is administered. Specifically, at a given time, after the compound is introduced into the patient's body, the tissue concentration difference of the compound between the normal tissue and the diseased tissue in the patient becomes 1 to 2.0 or more, more preferably 1 to 2.5 or more. period. As an example of the period during which the intratissue concentration difference of a compound between normal tissue and diseased tissue in a living body becomes 1 to 2.0 or more, more preferably 1 to 2.5 or more, the neutron capture cross-sectional area will be 1000barn (1000barn). ×10 ^-28 m ² ) The time after more than 3 hours have elapsed since a compound composed of a stable element of stable elements above 10 -28 m 2 ) was introduced into a living body.

The neutron diagnostic apparatus 100 uses a gamma ray camera installed around the patient to detect gamma rays generated by irradiating the patient with neutron NB. The gamma rays detected by the gamma ray camera are visualized in the analysis device.

As shown in FIG. 1 , the neutron diagnostic apparatus 100 includes a neutron generating unit 103; and γ-ray cameras 200-1 to 200-6. The neutron generating part 103 includes a neutron source 101 and a deceleration body 102.

In the first embodiment, a case of diagnosing PA, a patient with a brain tumor, will be described as an example. In FIG. 1 , the left picture shows the positional relationship between the patient PA and the gamma-ray cameras 200-1 to 200-6. In the left diagram of FIG. 1 , the neutron generating unit 103 is omitted. In Figure 1, the right figure is a schematic diagram showing the cross section A1-A2 in the left figure.

Neutron source 101 generates neutrons NB.

The decelerator 102 decelerates the neutrons NB generated by the neutron source 101 to the energy most suitable for diagnosis. The neutrons NB decelerated by the deceleration body 102 are irradiated to the patient PA. In the example shown on the right side of Figure 1, the patient PA is a patient with a brain tumor BT, so the head of the patient PA is irradiated with neutrons NB.

The γ-ray cameras 200-1 to 200-6 are respectively installed so as to surround the head of the patient PA. The γ-ray cameras 200-1 to 200-6 are respectively connected to the analysis device 300.

Hereinafter, any one of the γ-ray cameras 200-1 to 200-6 will be described as the γ-ray camera 200.

An example of the gamma ray camera 200 includes a radiation detector, a front-end circuit, a collection circuit, a shield, and a pinhole collimator.

Radiation detector detects incident gamma rays. An example of a radiation detector is a position-sensitive detector in which a plurality of radiation detection elements are arranged two-dimensionally (m×n matrix, m is an integer of m>0, n is an integer of n>0). As a plurality of radiation detection elements, for example, semiconductor elements such as silicon, germanium, CdTe, CdZnTe, TlBr, HgI ₂ , and GaAs can be used. When gamma rays are incident on a semiconductor element, the semiconductor element interacts with the gamma rays and outputs a pulse-like electronic signal to the front-end circuit. In addition, as a plurality of radiation detection elements, it is also possible to use optical elements (photomultiplier tubes, photodiodes, collapsed photodiodes, Geiger mode collapsed photodiodes, etc.) and NaI(Tl), CsI(Tl), Crystal scintillator combiner for GSO(Ce), LSO(Ce), BGO, etc.

The front-end circuit obtains the electronic signal output by the radiation detector, then pairs the obtained electronic signal with the component ID of the radiation detection component that detects the gamma ray, and then outputs it to the subsequent collection circuit. A plurality of radiation detection components are paired with existing component IDs. By pairing the electronic signal input from the radiation detector with the element ID of the radiation detection element that detects gamma rays, the radiation detection element that detects gamma rays can be specified in an m×n matrix.

The collection circuit sequentially performs preamplification processing, waveform shaping processing, peak hold processing, AD conversion processing, etc. on the electronic signal input from the front-end circuit, and converts it into digital peak information. The collection circuit accumulates peak information obtained by converting the electronic signal, and then outputs the accumulated peak information to the analysis device 300 . In the peak information, component ID, detection time, energy of radiation, etc. are related to each other.

The shielding body is used to prevent gamma rays passing through other than the incident hole from entering the radiation detector, and is made of a material with excellent ability to shield gamma rays, such as lead or tungsten. In addition, in the shielding body, a rectangular internal space is formed at the end of the side close to the measurement object of gamma rays, that is, the front end is provided with a pinhole collimator, and at the rear end of the formed internal space, Equipped with radiation detector.

The pinhole collimator is installed at the front end of the shielding body and has an incident hole (pinhole) in the center. In addition, the diameter of the incident hole can be adjusted, and the detection sensitivity and position resolution capability of gamma rays can be adjusted according to the diameter. As the diameter becomes narrower, the positional analysis capability tends to increase and the detection sensitivity tends to decrease.

The analysis device 300 receives the peak information respectively output by the gamma ray camera 200-1 to the gamma ray camera 200-6. The analysis device 300 specifies the incident direction of gamma rays corresponding to the element ID of the radiation detection element that detects gamma rays based on the element ID associated with the received peak information. Next, the analysis device 300, based on the peak information input from the gamma ray camera 200-1 to the gamma ray camera 200-6 respectively, Generate radiation information. Here, the position (arrangement) of the radiation detection elements is associated with the element ID in advance and stored in the memory unit.

The analysis device 300 may perform processing every time gamma rays are incident. By this, the count rate of each incident direction of γ-rays (each radiation detection element) can be calculated, that is, the number of detections of γ-rays per unit time.

Furthermore, the analysis device 300 creates a gamma-ray image based on the incident direction and count rate of gamma-rays. Here, the gamma ray image is, for example, an image that displays the incident direction of gamma rays in two dimensions and represents the incident amount of gamma rays in different tones.

Diagnosis is carried out by the following method.

A boron-containing molecular target diagnostic agent IA (hereinafter referred to as "boron probe") is administered to patient PA with brain tumor BT in advance. Boron probes are composed of stable elements, so there is no concern about internal exposure and there is no need to consider the half-life of the radioactive isotope. Boron probes accumulate in brain tumor BT, and their concentration in normal tissues decreases. Specifically, the boron probe is accumulated in the brain tumor BT. When 3 hours have passed after the boron probe is introduced into the patient's PA, the ratio of the concentration of the boron probe in the tumor to the concentration of the boron probe in the normal tissue becomes 2.0 or more. Than 1. Hereinafter, the period in which the intratissue concentration difference of the compound between normal tissue and diseased tissue is sufficiently high is called "Diagnostic Time Window". The diagnosis performed by the neutron diagnostic apparatus 100 is performed in the Diagnostic Time Window. The patient PA is directed to the neutron diagnostic device 100 .

Neutron source 101 generates neutrons NB. The neutron source 101 irradiates the generated neutrons NB during the first time, and then stops during the second time after irradiating the neutrons NB during the first time. After stopping during the second time period, the neutron source 101 irradiates again during the first time period. That is, the neutron source 101 repeats irradiation during the first time and stopping during the second time. An example of the first time is 0.1 seconds to 10 seconds. That is, the neutron source 101 performs pulse irradiation with a neutron NB irradiation time of 0.1 to 10 seconds. With this configuration, the exposure time of the neutron NB to the human body of the patient PA can be suppressed to the minimum required.

The neutron NB generated by the neutron source 101 is reduced to an energy level suitable for ^{the 10} B(n,α) ⁷ Li nuclear reaction through the decelerator 102, and is reduced to an energy level suitable for ^{the 10} B(n,α) ⁷ Li nuclear reaction. Neutron NB (neutron beam) reaches the brain tumor area where the boron probe is accumulated. After the neutron NB reaches the brain tumor area where the boron probe is accumulated, gamma rays are generated by the boron neutron capture reaction.

Figure 2 is a diagram illustrating the boron neutron capture reaction. The neutron beam NB reaches the brain tumor where the boron probe is accumulated, thereby causing a nuclear reaction between ¹⁰ B and neutrons. Because ¹⁰ B undergoes a nuclear reaction with neutrons, ⁴ He nuclei (α rays) and ⁷ Li atomic nuclei are released, further producing prompt γ rays of 478keV. Return to Figure 1 to continue the explanation.

The neutron diagnostic apparatus 100 detects generated γ-rays using the γ-ray cameras 200-1 to 200-6 located around the patient. The γ-ray cameras 200-1 to 200-6 respectively detect γ-rays that satisfy the condition that the sum of the scattering energy and the absorbed energy is 478keV±5%. The γ-ray cameras 200-1 to 200-6 output peak information to the analysis device 300.

The analysis device 300 receives peak information output from the gamma ray cameras 200-1 to 200-6 respectively, and creates a gamma ray image based on the received peak information. That is, the analysis device 300 derives the position where gamma rays are generated in the body of the patient PA based on the peak information output by the gamma ray camera 200-1 to the gamma ray camera 200-6 respectively, and creates a diagnostic report based on the derived position where gamma rays are generated. image.

(Neutron diagnostic method)

Fig. 3 shows an example of the operation of the neutron diagnosis method. Referring to FIG. 3 , the process of generating diagnostic images using the neutron diagnostic apparatus 100 will be described.

(step S1)

For patients with brain tumors BT PA puts in boron probes.

(step S2)

Determine whether the specified time has passed. That is, after inserting the boron probe into the patient PA, it is determined whether the Diagnostic Time Window has been reached. The Diagnostic Time Window has been reached, and the patient PA is guided to the neutron diagnostic apparatus 100 .

(step S3)

The neutron source 101 generates neutrons NB, repeatedly irradiates the generated neutrons NB during the first time period, and stops during the second time period. The neutron beam NB reaches the brain tumor area where the boron probe is accumulated, and generates gamma rays due to the boron neutron capture reaction.

(step S4)

The neutron diagnostic apparatus 100 detects generated γ-rays using the γ-ray cameras 200-1 to 200-6 located around the patient. The γ-ray cameras 200-1 to 200-6 output the peak information obtained by detecting the generated γ-rays to the analysis device 300. The analysis device 300 receives the peak information output by the gamma ray camera 200-1 to the gamma ray camera 200-6 respectively, and creates a gamma ray image based on the received peak information.

(Effects of the neutron diagnostic device according to the first embodiment)

The effect of the neutron diagnostic device 100 of the present embodiment is explained by comparing the diagnostic images obtained by the neutron diagnostic device 100 of the present embodiment with the images obtained by the PET diagnostic device.

FIG. 4 is a diagram showing an example of an image obtained by a PET diagnostic apparatus. In FIG. 4 , the concentration of the diagnostic agent is represented by the concentration of the color. Specifically, the color becomes darker depending on the concentration of diagnostic agents from weak to strong. In Figure 4, the input line amount is about 200MBq. In Figure 4, the part surrounded by a circle is the tumor. Outside of the tumor area, the densely colored area is around 2kBq/ml. That is, a high dose of gamma rays can be detected even in parts other than the tumor.

As can be seen from FIG. 4 , imaging is performed in a state where the diagnostic agent for PET examination remains in blood vessels and normal tissues. It is also known that imaging is performed in a state where the diagnostic agent is not completely accumulated in the tumor tissue. Therefore, it is impossible to determine whether it is a tumor based on gamma ray intensity alone, so diagnosis requires a high degree of experience and skill from the physician.

FIG. 5 is a diagram showing an example of an image obtained by the neutron diagnostic device according to this embodiment. In FIG. 5 , the concentration of the diagnostic agent is represented by the concentration of the color. Specifically, the color becomes darker depending on the concentration of diagnostic agent from weak to strong. In Figure 5, the thermal neutron beam is 1.0×10 ⁸ n/cm ² /sec. In addition, ^{the 10} B concentration is 100 ppm. In Figure 5, the part surrounded by a circle is the tumor. The tumor part is almost the same as the darker part, which is an area of about 2MBq/ml. Compared with Figure 4, a signal about 1000 times stronger appears.

As can be seen from FIG. 5 , imaging is performed in a state where the boron probe is concentrated in the tumor tissue. Because a clear diagnostic image of the tumor part is obtained, a correct diagnosis can be made without relying on the skill of the physician. In addition, tumors below 5 mm that cannot be detected by PET diagnosis can also be detected.

In the first embodiment described above, the case where the patient PA has a brain tumor has been described, but the invention is not limited to this example. For example, it can also be applied when the patient PA has a disease centered on cancer such as lung cancer and colorectal cancer.

In the first embodiment described above, the case where the neutron diagnostic apparatus 100 includes six gamma-ray cameras 200 has been described, but the invention is not limited to this example. For example, the number of gamma-ray cameras included in the neutron diagnostic apparatus 100 may be 1 to 5, or may be 7 or more.

In the first embodiment described above, the case of using a boron agent labeled with a specific substance using the stable element boron ( ¹⁰ B) is explained as a stable neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more. An example of a compound composed of stable elements of an element, but is not limited to this example. For example, the same applies to the case of using a gallium chemical labeled with gallium (Gd).

In the above-mentioned first embodiment, it can be determined by at least one of the intensity of the neutron beam NB output by the neutron source 101, the first time of irradiating the neutron NB, and the number of repetitions of the first time of irradiating the neutron NB. The intensity of gamma rays generated by the neutron diagnostic device 100 is adjusted. By adjusting the intensity of the generated γ-rays, the γ-ray image displayed in the analysis device 300 can be made suitable for observation.

According to the first embodiment, a compound composed of a stable element including a stable element with a large neutron capture cross-sectional area is introduced into a living body, the living body is irradiated with neutrons NB, and gamma rays generated by the neutron reaction are detected. In this embodiment, since a compound composed of a stable element is used as a diagnostic agent, it is possible to remove the restriction caused by the imaging period determined by the half-life of the radioactive isotope in the diagnostic agent for PET examination. By fully accumulating the diagnostic agent, By photographing the lesion during the period, a diagnostic image can be obtained that can clearly identify normal tissue. That is, since the time from injection to examination can be flexibly lengthened, the examination can be performed during a period when the diagnostic agent is sufficiently accumulated in the lesion and a concentration difference occurs between the lesion and the normal tissue. Therefore, inspection accuracy can be improved with or without the technology to interpret images.

In addition, by using compounds composed of stable elements, diagnostic reagents can be mass-produced and stored for a long period of time, so that low-cost diagnostic reagents can be stably supplied.

In addition, by using compounds composed of stable elements, internal radiation exposure and daily life restrictions caused by radioactive isotopes can be relieved.

In addition, there is no restriction on the amount of medicine injected due to internal radiation exposure, etc., so the medicine can be injected in the amount required for diagnosis.

In addition, since gamma rays are only generated when neutron NB is irradiated, there is no radiation exposure due to radioactive isotopes. In other words, since there is no internal radiation exposure, there is no limit to the amount of pharmaceutical input, and a concentration suitable for diagnosing the lesion can be injected.

Furthermore, by adjusting the intensity of the irradiated neutron rays, the intensity of the generated gamma ray source can be controlled to the optimum intensity for photography. That is, by controlling the neutron NB intensity, the resulting gamma ray intensity can be controlled, so the imaging conditions that enable observation can be set more clearly.

(Second implementation mode)

(Neutron Diagnostic Device)

6A and 6B are schematic diagrams showing an example of the neutron diagnostic device according to the second embodiment.

The neutron diagnostic device 500 in the second embodiment includes neutron sources 400-1 to 400-8, deceleration members 410-1 to 410-8, and γ-ray cameras 420-1 to 420 -16.

In the second embodiment, a case where the patient PA has a brain tumor will be described as an example. Figure 6A shows the positions between the patient PA, the neutron sources 400-1 to 400-8, the deceleration materials 410-1 to 410-8, and the gamma ray cameras 420-1 to 420-8. relation. FIG. 6B is a schematic diagram showing the cross section of B1-B2.

Neutron sources 400-1 to 400-8 are respectively arranged to surround the patient PA. Neutron sources 400-1 to 400-8 respectively generate neutrons and accelerate the generated neutrons.

The decelerating materials 410-1 to 410-8 respectively decelerate the neutrons generated by the neutron sources 400-1 to 400-8 to the energy most suitable for diagnosis. Each of the decelerating materials 410-1 to 410-8 is made of Teflon material. The patient PA is irradiated with neutrons decelerated by the deceleration members 410-1 to 410-8. In the example shown in FIG. 6A and FIG. 6B , the patient PA is a patient with the brain tumor BT, so the neutrons are irradiated toward the head of the patient PA.

Each of the γ-ray cameras 420-1 to 420-16 is installed to surround the patient PA. The γ-ray cameras 420-1 to 420-16 are respectively connected to the analysis device 300. In Figure 6A and Figure 6B The illustration of the analysis device 300 is omitted. The gamma ray camera 200 can be applied to the gamma ray camera 420-1 to the gamma ray camera 420-16 respectively.

Hereinafter, any neutron source among neutron sources 400-1 to 400-8 will be described as neutron source 400. Among the decelerating members 410-1 to 410-8, any decelerating member is described as decelerating member 410.

Diagnosis is performed in the following manner.

A boron probe was administered to PA, a patient with brain tumor BT, in advance. Boron probes accumulate in brain tumor BT and reduce the concentration in normal tissues. Specifically, the boron probe accumulates in the brain tumor BT, and when a period of more than 3 hours has elapsed since the boron probe was introduced into the patient PA and a Diagnostic Time Window has occurred, the concentration of the boron probe in the tumor is different from that of the boron probe in the normal tissue. The ratio of concentration becomes more than 2.0 to 1. Diagnosis by the neutron diagnostic device 100 is started only after more than 3 hours have elapsed since the boron probe was inserted into the patient's PA, that is, the Diagnostic Time Window. The patient PA is directed to the neutron diagnostic device 100 .

Neutron source 400 produces neutrons. The neutron source 400 irradiates the generated neutrons during the first time period, and then stops during the second time period after irradiating the neutrons during the first time period. The neutron source 101 irradiates during the first time period after stopping during the second time period. That is, the neutron source 400 repeats irradiation during the first time and stopping during the second time. Here, the first time is 0.1 seconds to 10 seconds. With this configuration, the exposure time of neutrons to the patient PA's human body can be suppressed to the necessary minimum.

The neutron beam generated in the neutron source 400 is reduced by the moderator 410 to ^an energy level suitable for ^{the 10 B} (n,α) ⁷ Li nuclear reaction. The neutron beam reaches the brain tumor where the boron probe is accumulated.

The neutron beam reaches the brain tumor where the boron probe is accumulated, and generates gamma rays through the neutron capture reaction of boron.

The neutron diagnostic apparatus 500 detects generated γ-rays using the γ-ray cameras 420-1 to 420-16 around the patient. The γ-ray cameras 420-1 to 420-16 respectively include a scatterer (not shown) and an absorber (not shown), and detect γ-rays that satisfy the condition that the sum of the scattering energy and the absorbed energy becomes 478keV±5%. . The γ-ray cameras 420-1 to 420-16 output peak information to the analysis device 300.

The analysis device 300 receives peak information output from the gamma ray cameras 420-1 to 420-16 respectively, and creates a gamma ray image based on the received peak information. That is, the analysis device 300 derives the position where gamma rays are generated in the patient's body based on the peak information output by the gamma ray cameras 420-1 to 420-16 respectively, and creates a diagnostic image based on the derived gamma ray generation positions.

(Neutron diagnostic method)

An example of the operation of the neutron diagnosis method will be described with reference to FIG. 3 .

In step S1, a boron probe is inserted into the patient PA having a brain tumor BT.

In step S2, it is determined whether a predetermined time has elapsed. That is, after inserting the boron probe into the patient PA, it is determined whether the Diagnostic Time Window has been reached. When the Diagnostic Time Window is reached, the patient PA is guided to the neutron diagnostic apparatus 500 .

In step S3, neutron sources 400-1 to 400-8 respectively generate neutrons, irradiate to generate neutrons during the first time, stop during the second time, and repeat the first time and the second time. time. The neutron beam reaches the brain tumor area where the boron probe is accumulated, and the neutron capture reaction of boron is carried out, thereby generating gamma rays.

In step S4, the neutron diagnostic apparatus 500 detects the generated γ-rays using the γ-ray cameras 420-1 to 420-16 around the patient. The γ-ray cameras 420-1 to 420-16 respectively output peak information obtained by detecting the generated γ-rays to the analysis device 300. Analysis device 300, then Receive the peak information output by the gamma ray camera 420-1 to the gamma ray camera 420-16 respectively, and create a gamma ray image based on the received peak information.

In the second embodiment described above, the patient has a brain tumor, but the invention is not limited to this example. For example, it can be applied to a case where the patient has a disease centered on cancer such as lung cancer and colorectal cancer.

In the second embodiment described above, the case where the neutron diagnostic apparatus 500 includes 16 gamma-ray cameras 420 has been described, but the invention is not limited to this example. For example, the number of gamma-ray cameras included in the neutron diagnostic apparatus 500 may be 1 to 15, or may be 17 or more.

In the second embodiment described above, the case of using a boron agent that labels a specific substance with the stable element boron ( ¹⁰ B) is explained as a stable element containing a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more. An example of a compound composed of stable elements, but is not limited to this example. For example, the same applies to the case of using a gallium chemical labeled with gallium (Gd).

In the above second embodiment, the intensity of the gamma rays generated by the neutron diagnostic device 500 can be determined by the intensity of the neutron beam output by the neutron source 400, the first time of neutron irradiation, and the first time of neutron irradiation. At least one of the number of repetitions of the time is adjusted. By adjusting the intensity of the generated γ-rays, the γ-ray image represented by the analysis device 300 can be made suitable for observation.

According to the second embodiment, a compound composed of a stable element with a large neutron capture cross-sectional area is introduced into a living body, the living body is irradiated with neutrons, and gamma rays generated by the neutron reaction are detected. With this configuration, since a compound composed of a stable element is used as a diagnostic agent, the imaging period is not limited by the conventional half-life of the radioactive isotope in the diagnostic agent for PET examination, and the diagnostic agent can be fully accumulated in the PET examination. By photographing the lesion during the period, a diagnostic image can be obtained that can clearly identify normal tissue. That is, it is possible to flexibly lengthen the time from input to examination, etc., and it is possible to target diagnosis. The examination is performed during the period when the drug is sufficiently accumulated in the lesion to create a concentration difference between normal tissues. Therefore, inspection accuracy can be improved regardless of whether one has the technology to interpret images.

Furthermore, by using compounds composed of stable elements, diagnostic reagents can be mass-produced and stored for a long period of time, and low-cost diagnostic reagents can be stably provided.

In addition, because of the use of compounds composed of stable elements, internal radiation exposure or life restrictions caused by radioactive isotopes can be eliminated.

In addition, there are no restrictions on the amount of pharmaceuticals injected due to internal radiation exposure, etc., so the pharmaceuticals can be injected in the amount required for diagnosis.

Furthermore, because gamma rays are only produced when irradiated with neutrons, there is no radiation exposure due to radioactive isotopes. In other words, since there is no internal radiation exposure, there is no limit to the amount of pharmaceutical input, and a concentration suitable for diagnosing the lesion can be injected.

Furthermore, by adjusting the intensity of the irradiated neutron rays, the intensity of the generated gamma ray source can be controlled to the optimum intensity for photography. That is, since the intensity of neutrons can be controlled to control the intensity of the resulting gamma rays, imaging conditions that enable clearer observation can be set.

<Configuration example>

As an example of the structure, the neutron diagnostic device includes a compound composed of a stable element including a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, and a decelerator that decelerates the neutrons (implemented). In this embodiment, the decelerator 102 and the decelerating members 410-1 to 410-8 are provided with a neutron generating unit (in an embodiment, they are a neutron generating unit 103), and a gamma ray detection unit that detects gamma rays (in the embodiment) The neutron diagnostic device (in the embodiment, the neutron diagnostic device 100, the neutron diagnostic device 100, the γ ray camera 420-1 to the γ ray camera 420-16), Device 500), which includes: a neutron source (in the embodiment, the neutron source 101, the neutron source 400-1 to the neutron source 400-8), after the compound is put into the living body as the observation object, the compound The living body is irradiated with neutrons during a period during which a predetermined concentration difference in the tissue is generated between the normal tissue and the diseased tissue in the living body (Diagnostic Time Window in the embodiment); the output unit observes the gamma ray detection unit The output of gamma rays emitted by the reaction of elements contained in the compound with neutrons in a living body that has been irradiated by neutrons.

As an example of a configuration, in a neutron diagnostic device, a compound introduced into a living body and a molecular target substance bonded to a specific human molecule are bonded or contain a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) The above stable elements, and the compounds are absorbed or accumulated in the diseased parts of the living body.

As a structural example, in a neutron diagnostic device, the stable element contained in the compound and having a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more is boron (B) or gallium (Gd).

As one structural example, in the neutron diagnostic apparatus, the neutron source performs pulse irradiation with a neutron irradiation time of 0.1 to 10 seconds.

As an example of a configuration, in a neutron diagnostic device, the compound injected into the living body contains a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, and its concentration is higher than that found in nature. The content ratio of isotopes.

As an example of a configuration, in a neutron diagnostic device, the neutron source is located more than 3 hours after the compound containing a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more is introduced into the living body. Then irradiate neutrons.

As one structural example, in the neutron diagnostic device, the neutron source is a period during which the intratissue concentration difference of the compound between the normal tissue and the diseased tissue in the injected living body becomes 1 to 2.0 or more after the compound is injected into the living body. , irradiate neutrons.

As one structural example, in the neutron diagnostic device, either or both of the glucose absorbed by the tumor tissue and the glucose accumulated in the tumor tissue is bonded or contains a neutron capture interception among the compounds injected into the living body. Stable elements with an area above 1000barn (1000×10 ^-28 m ² ).

As an example of the configuration, in the neutron diagnostic device, the compound injected into the living body includes a boron-containing compound; among the molecular target substances bonded to specific molecules of the human body; or glucose absorbed by the tumor tissue and glucose accumulated in the tumor tissue. Glucose, either or both, is bonded to or contains one or more boron-containing compounds.

Although the embodiments have been described above, these embodiments are only provided as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, changes, and combinations can be made without departing from the spirit of the invention. These embodiments, while being included in the scope and gist of the invention, are also included in the scope of the invention described in the patent application and their equivalent scope.

100:Neutron diagnostic device

101:Neutron Source

102: Reducer

103: Neutron Generation Department

200-1~200-6: γ-ray camera

300:Analysis device

NB: Neutron

BT: brain tumor

PA:patient

IA: Boron-containing molecular target diagnostic agent

Claims (9)

A neutron diagnostic device, including a compound composed of a stable element containing a stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, a neutron generating part including a decelerator that decelerates neutrons, As well as a gamma ray detection unit for detecting gamma rays, the neutron diagnostic device further includes: a neutron source. After the compound is injected into the living body as the observation object, the compound is detected in the normal tissue and the living body in which the compound is injected. During the period when a predetermined tissue concentration difference occurs between the diseased tissues, the living body is irradiated with neutrons; and the output unit uses the gamma ray detection unit to observe the living body that has been irradiated with the neutrons because the elements contained in the compound are different from the The resultant output of gamma rays emitted by the neutron reaction. The neutron diagnostic device according to claim 1, wherein the compound injected into the living body, among the molecular target substances bonded to specific molecules of the human body, has a bonded or contained neutron capture cross-sectional area of 1000 barn (1000 ×10 ^-28 m ² ) or more, and the compound is absorbed or accumulated in the lesion of the living body. The neutron diagnostic device as described in claim 1, wherein the stable element containing the neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more in the compound is boron (B) or gallium (Gd) . The neutron diagnostic device according to claim 1, wherein the neutron source performs pulse irradiation with a neutron irradiation time of not less than 0.1 seconds and not more than 10 seconds. The neutron diagnostic device as described in claim 1, wherein the compound put into the living body has a proportion of the stable element with a neutron capture cross-sectional area of 1000barn (1000×10 ^-28 m ² ) or more, and its concentration Higher than the content ratio of isotopes found in nature. The neutron diagnostic device as described in claim 1, wherein the neutron source is after the compound containing the stable element with a neutron capture cross-sectional area of more than 1000barn (1000×10 ^-28 m ² ) is put into the living body The neutrons were irradiated after more than 3 hours. The neutron diagnostic device according to claim 1, wherein the neutron source is a tissue concentration of the compound between the normal tissue and the diseased tissue in the injected living body after the compound is injected into the living body. During the period when the difference becomes 1 to 2.0 or more, the neutrons are irradiated. The neutron diagnostic device according to claim 1, wherein the compound injected into the living body bonds with either or both of glucose absorbed by the tumor tissue and glucose accumulated in the tumor tissue. Or contain the stable element with the neutron capture cross-sectional area above 1000barn (1000×10 ^-28 m ² ). The neutron diagnostic device according to claim 1, wherein the compound injected into the living body is a boron-containing compound, a molecular target substance bonded to a specific molecule of the human body, or glucose and glucose absorbed by the tumor tissue. Either or both of the glucose accumulated in the tumor tissue are bound to or contain one or more boron-containing compounds.

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