JP5799388B2 - Cancer treatment system - Google Patents

Description

  The present invention relates to a cancer treatment system for treating cancer using radiation.

  As a method for treating cancer, a method of destroying cancer cells using radiation is known. As such a treatment method, for example, a method of irradiating the affected part with a particle beam (proton beam, carbon beam or heavy particle beam) accelerated as an ion by an accelerator is used. In this treatment method, since the particle beam also has an adverse effect on healthy cells, the position and energy of the beam are set so that the particle beam is intensively applied to the affected part (site with cancer). . However, it is actually difficult to selectively irradiate the affected part with the particle beam.

Boron Neutron Capture Therapy (BNCT) is known as a treatment method that improves this point. BNCT is described in Non-Patent Document 1, for example. In BNCT, first, a boron ( ¹⁰ B) compound that easily collects in cancer cells in the body is administered to a patient. Thereafter, the affected area is irradiated with a neutron beam. ^{Since 10} B has a large neutron absorption cross-sectional area, the ¹⁰ B (n, α) ⁷ Li reaction is generated by this neutron. That is, α particles and Li nuclei are generated by irradiation with a neutron beam. These α particles and Li nuclei function as the particle beam (heavy particle beam). That is, cancer cells are destroyed by α particles and Li nuclei generated by the reaction between ¹⁰ B and neutrons. As the neutron beam, for example, one generated from a nuclear reactor can be used. Moreover, since control of the neutron beam emitted from the nuclear reactor is not easy, Patent Documents 1 and 2 describe accelerators suitable for generating the neutron beam. That is, it is possible to more easily control neutron beams using such an accelerator.

In this method of treatment, (1) ¹⁰ B tends to collect in the vicinity of cancer cells, and (2) the range of α particles and Li nuclei in the body is short. Li nuclei can be irradiated. That is, cancer cells can be irradiated with these particles with high selectivity. In this treatment method, it is not the irradiated neutron beam but the α particles and Li nuclei generated by the nuclear reaction that directly affect the cancer cells. When destroying cancer cells with a particle beam, heavier particles can absorb more energy than light particles, and both double-stranded DNAs in the cancer cells can be destroyed. Probability is high. For this reason, the effect which destroys a cancer cell is large compared with the case where a proton beam etc. are used.

  That is, BNCT can be used to destroy cancer cells in the body with high selectivity with normal cells.

JP 2007-95553 A JP 2010-287419 A

Japan Atomic Energy Agency HP, June 26, 2006, Document 2, [Search July 22, 2011], Internet (URL: http://www.jaea.go.jp/02/press2006 /P06062601/t2.pdf)

  However, a particle beam such as a proton beam is generally generated as a beam in the form of a charged ion, and it is easy to electromagnetically control this beam, whereas a neutron has no charge. Compared with proton beams and the like, it is extremely difficult to control the beam. On the other hand, the size of a portion (malignant tumor) having cancer cells to be destroyed by BNCT is often about several mm. For this reason, in the above BNCT, it is difficult to selectively irradiate the affected part with a neutron beam with a sufficiently small beam diameter. On the other hand, neutrons have an adverse effect on healthy cells. For this reason, it has been difficult to destroy cancer cells with high selectivity even by BNCT.

  That is, it has been difficult to obtain a cancer treatment system that can destroy cancer cells with high selectivity.

  The present invention has been made in view of such problems, and an object thereof is to provide an invention that solves the above problems.

In order to solve the above problems, the present invention has the following configurations.
The cancer treatment system of the present invention comprises a drug administration means for administering to a patient a drug that contains a nuclide that generates heavy particles by absorbing gamma rays and accumulates in a place where cancer cells are present, and the drug is administered. Gamma ray irradiation means for irradiating a gamma ray beam having energy for generating the heavy particles in the nuclide to the patient.
In the cancer treatment system of the present invention, the gamma ray irradiation means is a laser Compton gamma ray source.
The cancer treatment system of the present invention is characterized in that, in the laser Compton gamma ray source, electrons that circulate in a closed orbit are used, and the gamma rays are extracted from a plurality of locations in the closed orbit.
The cancer treatment system of the present invention is characterized in that, in the laser Compton gamma ray source, electrons traveling in an open orbit are used and the gamma rays are extracted from a plurality of locations in the open orbit.
In the cancer treatment system of the present invention, the nuclide includes at least one of ¹⁹ F, ¹⁷ O, and ¹⁸ O.
In the cancer treatment system of the present invention, the drug is mainly composed of FDG (fluorodeoxyglucose).
The cancer treatment system of the present invention is characterized in that ¹⁸ F is added to the drug.

  Since the present invention is configured as described above, cancer cells can be destroyed with high selectivity.

It is a figure showing an outline of composition of a cancer treatment system concerning an embodiment of the invention. It is a figure which shows the condition of the reaction in which the nuclide administered to the patient absorbs gamma rays in the cancer treatment system according to the embodiment of the present invention. It is a figure which shows typically the condition at the time of ¹⁹ F absorbing a gamma ray in a body. It is a figure which shows an example of a structure of a laser Compton gamma ray source. It is a block diagram which shows the detail of the gamma ray generation part in a laser Compton gamma ray source. It is a figure which shows typically the result of having compared the energy absorption density in the body by the cancer treatment system which concerns on embodiment of this invention with particle beam irradiation and X-ray irradiation.

  Hereinafter, a cancer treatment system according to an embodiment of the present invention will be described. FIG. 1 is a diagram showing the configuration of this cancer treatment system. In this cancer treatment system, drug administration means 10 and gamma ray irradiation means 20 are used.

  FIG. 1 shows an example in which cancer treatment is performed on three patients A, B, and C. In patients A, B, and C, affected areas A1, B1, and C1 having cancer cells are different sites. As shown in the upper side of FIG. 1, the drug administration means 10 administers a drug 11 containing a specific isotope to patients A, B, and C, for example, by injection or the like. As the medicine 11, a medicine that easily gathers in the affected areas A 1, B 1, C 1 in the body of the patients A, B, C is used. For this reason, the drug 11 is accumulated in each affected part A1, B1, C1 after administration. This is the same as the above BNCT. Specific contents of the medicine 11 will be described later.

  Next, as shown in the lower side of FIG. 1, gamma rays 21 emitted from the gamma ray irradiating means 20 are irradiated to the affected areas A1, B1, and C1 in the patients A, B, and C in which the drug 11 has accumulated in the affected area. Here, it is possible to irradiate gamma rays 21 in a plurality of directions simultaneously from a single gamma ray irradiating means 20. For this reason, this irradiation can be performed simultaneously on the patients A, B, and C. Details of the gamma ray irradiation means 20 will be described later.

First, the drug 11 administered here will be described. The drug 11 administered here includes an isotope that generates heavy particles by absorbing gamma rays 21. The heavy particles referred to here are particles having a weight equal to or greater than that of protons, and specifically mean protons, neutrons, α particles, and various atomic nuclei. The main elements constituting the human body include H, O, C, N, Ca, etc., but isotopes of elements not belonging to these are preferred as the isotopes. For example, ¹⁹ F which emits α particles and ¹⁵ N nuclei by absorbing gamma rays 21 is effective as this isotope.

Specifically, FDG (fluorodeoxyglucose) to which ¹⁹ F is added can be used as the drug 11 that contains ¹⁹ F and easily accumulates in the affected area. FDG is a drug administered when diagnosis is performed by PET (positron tomography), and one of glucose groups of glucose in glucose is substituted with a nuclide that emits positrons (positrons). Usually, ¹⁸ F is particularly preferably used as this nuclide. In PET, FDG to which ¹⁸ F is added accumulates in the affected area (site with cancer cells), and the distribution of cancer cells is detected by detecting gamma rays generated by the annihilation of positrons and electrons emitted from ¹⁸ F. taking measurement. As the drug 11 used here, one obtained by substituting ¹⁸ F in this FDG with ¹⁹ F can be preferably used. This substitution is easy because ¹⁸ F and ¹⁹ F have similar chemical properties.

For example, the ¹⁹ F nucleus is excited by resonance absorption of gamma rays 21 having an energy of 6088 keV. After that, it decays into α particles ( ⁴ He nuclei) and ¹⁵ N nuclei. The relationship of energy levels in this nuclear reaction is shown on the left side of FIG. 2, and the spectrum of the gamma ray 21 corresponding thereto is schematically shown on the right side of FIG. That is, this nuclear reaction can be selectively generated by irradiating the quasi-monochromatic gamma ray 21 whose spectrum peak is equal to the excitation energy.

As schematically shown in FIG. 3, when ¹⁹ F nuclei 100 absorb gamma rays 21 of this energy, α particles 101 and ¹⁵ N nuclei 102 are generated. The α particles 101 and the ¹⁵ N nuclei 102 destroy the DNA 202 in the cell nucleus 201 in the nearby cancer cell 200. The α particles 101 and ¹⁵ N nuclei, which are heavy particles, have a large energy per unit volume, and have a high probability of destroying both the double helical structures of the DNA 202. This effect is particularly significant at larger ¹⁵ N nuclei. That is, the cancer cell 200 can be destroyed similarly to BNCT. At this time, because (1) FDG ( ¹⁹ F) tends to gather in the vicinity of cancer cells, and (2) the range of α particles 101 and ¹⁵ N nuclei 102 in the body is short, cancer cells are particularly efficient. Similar to BNCT, it can be destroyed.

  However, here, gamma rays are used instead of neutron beams in BNCT. The advantages of using gamma rays are that it is easy to irradiate a specific region locally, that it is possible to irradiate deeper parts of the body, and that a single irradiation device (gamma irradiation unit 20) is used. It is possible to irradiate a large number of patients at the same time. Below, the specific structure of the gamma ray irradiation means 20 is demonstrated.

  As the gamma ray irradiation means 20, a device capable of emitting a monochromatic or quasi-monochromatic gamma ray 21 corresponding to the resonance absorption energy of the isotope nucleus contained in the drug 11 is used. As such a gamma ray irradiation means 20, a laser Compton gamma ray source is particularly preferably used.

  FIG. 4 is a diagram showing the configuration of the laser Compton gamma ray source 50. In the laser Compton gamma ray source 50, high energy electrons orbit around the closed orbit, and energy is transferred from the high energy electrons to the irradiated laser light (visible light, etc.), so that the laser light becomes high energy and gamma rays. It becomes. The laser light is monochromatic, but the gamma rays are quasi-monochromatic whose energy is determined according to the energy of the electrons. For this reason, it is possible to adjust the energy of gamma rays by adjusting the energy of electrons. This configuration is the same as that described in, for example, Japanese Patent Application Laid-Open No. 2003-232892.

  In FIG. 4, a relatively low energy electron beam incident from an injector 51 is deflected by an incident deflecting magnet (not shown) and is put on a predetermined electron trajectory. By providing a plurality of deflecting magnets 52 in the electron trajectory, the electrons are set to form a predetermined electron trajectory (closed trajectory). In this configuration, the electron trajectory is set to be bent by eight deflecting magnets 52. In addition, a high frequency (RF) acceleration cavity 53 is provided at a position where the trajectory is a straight line between the deflection magnets 52, and electrons are accelerated by a high frequency electric field in the high frequency acceleration cavity 53, and the electrons are increased in energy. Or the energy which an electron loses with the oscillation of a gamma ray or synchrotron radiation is replenished. At this time, the high frequency used in the high frequency acceleration cavity 53 is set so that the trajectory of electrons is maintained. In addition, in order to annihilate this high energy electron at the end of operation, the electron is set to be absorbed by the beam dump 54 off the above-mentioned closed orbit. This configuration is the same in an electron synchrotron, an electron storage ring for generating radiation light, and an energy recovery type linac.

  In this laser Compton gamma ray source 50, gamma ray generators 60 are installed at six locations corresponding to locations where electrons are deflected or straight portions. FIG. 5 is a block diagram showing the configuration of the gamma ray generation unit 60 in more detail, and particularly shows the configuration of the gamma ray generation unit 60 surrounded by the broken line at the upper left in FIG. As described above, the high-energy electron beam 70 travels in the direction indicated by the black arrow in FIG. On the other hand, a laser light source 80 is provided, and laser light 81 that is visible light is emitted. The laser beam 81 is reflected by the reflecting mirror 82 and is set to collide frontward with the electron beam 70 at the collision point P on the linear trajectory of the electron beam 70.

  The laser beam 81 receives energy from high-energy electrons by the (reverse) Compton effect at the time of the collision, and increases the energy. As a result, gamma rays 21 are emitted in a direction along the linear trajectory of the electron beam 70. The gamma rays 21 are extracted through the deflecting magnet 52 and the reflecting mirror 82. The electrons in the electron beam 70 lose energy due to this collision, but this amount of energy is replenished by the high-frequency acceleration cavity 53.

  The gamma ray generator 60 is provided corresponding to the deflection magnet 52 or the straight line portion. For this reason, in the configuration of FIG. 4, the gamma ray generation units 60 are provided at six places where the directions in which the gamma rays 21 are emitted are different. That is, six independent gamma rays 21 can be extracted from a single laser Compton gamma ray source 50. For this reason, even if the gamma ray source (laser Compton gamma ray source 50) and its maintenance are expensive, the cost required for treatment can be reduced. This effect becomes more prominent as more gamma ray generation units 60 are provided.

  In addition, an accelerator that can generate a high-energy electron and collide it with laser light to generate a laser Compton gamma ray is the same even if the electron is not an accelerator that forms a closed orbit. For example, in a linac in which electrons form an open orbit, laser Compton gamma rays can be generated similarly, and a plurality of gamma ray generation units can be provided.

  When the electron beam 70 and the laser beam 81 are collided in front, the gamma ray 31 has a sharp directivity with the traveling direction of the electron beam 70 as a peak. In addition, the spectrum has a divergence angle dependency, but has a narrow energy band that can be regarded as a quasi-monochromatic color. Further, the collision between the electron beam 70 and the laser beam 81 can be set slightly deviated from the frontal collision. In this case as well, a quasi-monochromatic spectrum can be obtained. The energy of this peak can be set by adjusting the energy of electrons, and as shown on the right side of FIG. 2, the peak can be adjusted to the resonance energy of the nucleus.

  In addition, unlike the neutron beam, since the directivity of the emitted gamma ray 21 is strong, it is easy to irradiate a specific region in the two-dimensional plane, and it is also easy to irradiate the affected area locally. is there. For this purpose, it is preferable to accurately control the positions of the patients A, B, and C in a state where the position of the gamma ray generator 60 and the direction in which the gamma rays 21 are emitted are fixed. The on / off control of the gamma ray 21 is easily performed by turning on / off the laser beam 81 and the electron beam 70. For this reason, the bad influence with respect to normal cells other than a cancer cell can be reduced more compared with the conventional BNCT.

  Conventionally, irradiation of gamma rays, X-rays, and particle beams has been performed as a cancer treatment method. In these cases, the absorbed energy per unit volume can be taken as a measure for destroying cancer cells. That is, the greater the absorbed energy, the greater the therapeutic effect at the location where cancer cells are present. On the contrary, it is preferable to reduce the absorbed energy at a place where cancer cells do not exist. FIG. 6 is a diagram schematically showing the distribution of absorbed energy from the surface of the body. Here, the dotted line indicates a high-energy particle beam, the broken line indicates an X-ray or a low-energy gamma ray, and the solid line indicates a case of the above cancer treatment system.

  In a normal high energy particle beam (dotted line), the region where the particle finally stays has a certain depth. For this reason, the distribution of the absorbed energy also corresponds to this and has a distribution having a peak at a certain depth. However, the absorbed energy before reaching the peak depth is not negligible and is about 1/2 to 1/3 of the peak value. For this reason, the adverse effect on normal cells cannot be ignored.

  Further, when X-rays or low-energy gamma rays are simply irradiated (broken line), the absorbed energy near the surface is large, and the absorbed energy decreases as it progresses into the body.

On the other hand, in the above cancer treatment system, first, it can be considered that the nuclide contained in the drug 11 is present in an extremely small amount other than the affected part. Therefore, the gamma ray 21 is absorbed at a depth until the affected part is present. Is small. However, when the gamma ray 21 reaches the affected area, it is absorbed by the nuclide ( ¹⁹ F) contained in the drug 11 to generate α particles 101 and ¹⁵ N nuclei 102, which are absorbed in the vicinity of the affected area. For this reason, when the above cancer treatment system is used, the absorbed energy has a sharp distribution that is particularly high in the affected area in the body. That is, when the above cancer treatment system is used, energy can be given with high selectivity to the affected part even in the depth direction in the body. Further, this energy corresponds to the energy of the gamma ray 21, but this energy can be adjusted by the electron beam 70 or the laser beam 81.

Further, in conventional BNCT, ¹⁴ N, which is present in large amounts in the body, may react with neutrons to form ¹⁴ C. ¹⁴ C is a long-lived radioisotope and causes internal exposure. In the above cancer treatment system, ¹⁴ C is not generated. That is, also from this viewpoint, it is possible to reduce adverse effects on other than cancer cells compared to BNCT.

As described above, as the drug 11, FDG to which ¹⁹ F is added is preferably used. On the other hand, FDG to which ¹⁸ F, which is a positron emitting nuclide, is added is widely used in PET diagnosis, and by examining the positron emitted from ¹⁸ F, a site with cancer cells can be detected. ^{Since 18} F and ¹⁹ F are both fluorine isotopes and have similar chemical properties, it is also possible to use FDG to which these are added simultaneously. In this case, it is possible to destroy cancer cells by the above cancer treatment system immediately after confirming the presence of cancer by performing PET diagnosis.

In the above example, the case where FDG to which ¹⁹ F is added is administered to a patient as the drug 11 is described. However, other nuclides can be used instead of ¹⁹ F. As such nuclides, those having nuclei that are excited by absorbing gamma rays having resonance energy and then cause a nuclear reaction that releases heavy particles are preferable. At this time, the time from the excited state to the release of heavy particles is a short time of about femtoseconds to nanoseconds. For this reason, heavy particles are emitted substantially immediately after irradiation with gamma rays.

Since the heavy particles are preferably generated only in the vicinity of the affected area, the nuclide preferably has a small existence ratio in the human body. Specifically, ⁶ Li, ⁷ Li, ⁹ Be, ¹⁰ B, ¹¹ B, ¹⁵ N, ¹⁷ O, ¹⁸ O, or the like can be used. Here, an extremely large amount of oxygen is present in the human body, but the natural isotope abundance ratios of ¹⁷ O and ¹⁸ O are as small as 0.038% and 0.205%, respectively. For this reason, the chemical | medical agent 11 which concentrated ¹⁷ O, ¹⁸ O about 100 times, for example can be used. At present, ¹⁸ O is also used for PET, so it is possible to obtain a material having a concentration of nearly 100% at low cost, and it is also possible to obtain ¹⁷ O at low cost. Moreover, since the chemical properties of ¹⁷ O and ¹⁸ O are the same as those of ordinary oxygen, there are few adverse effects on the human body.

Table 1 shows the resonance energy (excitation energy) E, spin and parity of these nuclides, the type of transition in this excitation, Γ _T (probability of emitting heavy particles from the excited state: _expressed in energy dimension), Γ _γ0 (excitation) The probability of returning to the ground state by emitting one gamma ray from the state (shown in the dimension of energy), Γ _T / E, and the generated nuclide (particle) are shown. Here, E corresponds to the (peak) energy of gamma rays to be irradiated. Further, Γ _T >> Γ _γ0 is preferable from the viewpoint of efficiently generating heavy particles. Further, the resonance absorption tends to occur by gamma energy in the range of E ± Γ _T. Accordingly, the larger the Γ _T / E is, the more preferable the reaction itself is. However, the selectivity with other nuclides and other levels deteriorates, and this may cause the generation of heavy particles and gamma rays outside the affected area. There is a case. Therefore, the upper limit of Γ _T / E is preferably about 10%. The energy of the gamma ray 21 is set according to the nuclide used, and this setting is made by adjusting the energy of the electron beam 70 in the laser Compton gamma ray source 50 and the wavelength of the laser beam 81.

In addition to FDG, the substance that is likely to be accumulated in the affected area as the main component of the drug 11 can be set as appropriate according to the nuclide. For example, when ¹⁰ B and ¹¹ B, which are boron isotopes, are used, BSH (Na ₂ B ₁₂ H ₁₁ SH), which is also used for BNCT, can be used. BPA (paraborophenylalanine) can also be used in the same manner. Obviously, the use of ¹⁰ B or ¹¹ B as boron in these substances has the same effect as the above FDG. In addition, as the main component of the drug 11, a substance that can be administered to the human body and easily accumulates in the affected area can be appropriately selected and used.

  In the above example, the case where a laser Compton gamma ray source is used as the gamma ray generating means has been described. However, any gamma ray source capable of emitting monochromatic or quasi-monochromatic gamma rays can be used in the same manner. As an example, a gamma ray source that emits particles or neutron capture gamma rays or bremsstrahlung gamma rays can also be used.

DESCRIPTION OF SYMBOLS 10 Drug administration means 11 Drug 20 Gamma ray irradiation means 21 Gamma ray 50 Laser Compton gamma ray source 51 Injector 52 Deflection magnet 53 Radio frequency (RF) acceleration cavity 54 Beam dump 60 Gamma ray generation part 70 Electron beam 80 Laser light source 81 Laser light 82 Reflective mirror 100 ¹⁹ F nucleus 101 α particle 102 ¹⁵ N nucleus 200 Cancer cell 201 Cell nucleus 202 DNA
A, B, C Patient A1, B1, C1 Affected part P Collision point

Claims (7)

A drug administration means for administering to a patient a drug that contains a nuclide that generates heavy particles by absorbing gamma rays and accumulates in a location where cancer cells are present;
A cancer treatment system comprising: gamma ray irradiation means for irradiating a gamma ray beam having energy for generating the heavy particles on the nuclide to a patient to whom the drug is administered.   The cancer treatment system according to claim 1, wherein the gamma irradiation means is a laser Compton gamma ray source.   3. The cancer treatment system according to claim 2, wherein the laser Compton gamma ray source uses electrons that circulate in a closed orbit to extract the gamma rays from a plurality of locations in the closed orbit.   3. The cancer treatment system according to claim 2, wherein the laser Compton gamma ray source uses electrons that travel in an open orbit, and the gamma rays are extracted from a plurality of locations in the open orbit. 5. The cancer treatment system according to claim 1, wherein the nuclide includes at least one of ¹⁹ F, ¹⁷ O, and ¹⁸ O. 6.   The cancer treatment system according to claim 5, wherein the drug contains FDG (fluorodeoxyglucose) as a main component. The cancer treatment system according to claim 6, wherein ¹⁸ F is added to the drug.

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