JPH0513475B2 - - Google Patents

Description

[Detailed description of the invention]

[Field of the Invention] The present invention relates to an autoradiographic recording method, a stimulable phosphor sheet, and a stimulable phosphor sheet laminate used in the method. More specifically, the present invention can be effectively used to separate, identify, etc. a living body or a sample made of a living body-derived substance to which a radioactive label has been attached by obtaining positional information of the substance. The present invention relates to an autoradiographic recording method, a stimulable phosphor sheet, and a stimulable phosphor sheet laminate used in the method. [Technical Background of the Invention and Prior Art] After administering a radioactively labeled substance to an organism, the organism or a part of the tissue of the organism is used as a sample, and this sample is exposed to highly sensitive X-rays. An autoradiographic technique that consists of overlapping a radiation film such as a film for a certain period of time to sensitize (or expose) the film and obtain positional information of a radiolabeled substance in the sample from the exposed area. The autoradiographic measurement method (also called radioautography) is known from the prior art. This autoradiography is used, for example, to study in detail the metabolism, absorption, and excretion routes and conditions of administered substances in living organisms. ing. Biochemistry Experiment Course 6 Tracer Experiment Method (Part 1) 271
~289 pages, “8. Autoradiography” Toru Sueyoshi,
Akiyo Shigematsu (1977, published by Tokyo Kagaku Dojin Co., Ltd.) In recent years, autoradiography has been used to attach radioactive labels to polymeric substances derived from living organisms, such as proteins and nucleic acids, and then analyze the high It is also effectively used to obtain positional information of a radiolabeled substance on a support medium obtained by separating and developing a molecular substance, its derivative, or its fragment by gel electrophoresis or the like. Methods for separating and identifying polymeric substances, or evaluating their molecular weights and properties based on the positional information have also been developed and are in actual use. Furthermore, autoradiography using the 20-label method (double tracer method) using two types of radioisotopes has also been proposed in order to elucidate, for example, metabolic pathways in living organisms. That is, radiolabeled substances labeled with two or more different radioactive isotopes are administered to an organism at different times, and an autoradiograph is obtained for each radiolabeled substance (that is, for each radioisotope). Attempts are being made to elucidate the chemical reactions in living organisms by obtaining them. As a radiation film for autoradiography using such a double labeling method, for example, Japanese Patent Publication No. 47-45540 discloses a film containing couplers of different hues in two emulsion layers of silver halide. A silver halide photographic light-sensitive material for color autoradiography is disclosed for separately recording distribution images of tritium ( ³ H) and other radioactive isotopes by adjusting the layer thickness of the emulsion layer. There is. However, in autoradiography using conventional radiographic methods, it is very difficult to obtain autoradiographic images of samples that are multiplexed with different radioisotopes for each isotope. Even if a radiographic film such as the one described above is used, each autoradiographic image is visualized and recorded as a pigment image with a different color development on a single radiographic film, so researchers have to pay attention to the differences in hue. Only then do individual autoradiographic images have to be distinguished and analyzed.
Furthermore, since different autoradiographic images are recorded on a single radiation film, there is a problem in that it is not possible to obtain positional information of a radiolabeled substance in a sample with high precision. Furthermore, there are several problems when actually using autoradiography. First, in order to obtain an autoradiograph of a sample containing a radiolabeled substance, the sample and a radiation film such as a high-sensitivity X-ray film are overlapped for a certain period of time, and the film is exposed to light. However, this exposure operation requires a long time (several tens of hours to several days). This is because samples to be measured by autoradiography generally do not have high radioactivity. Second, this exposure operation typically must be performed at low temperatures (eg, 0°C to -80°C). The reason for this is that at relatively high temperatures such as room temperature, the latent image in the silver salt tends to regress on the film formed by exposure to radiation or fluorescence, resulting in an image that cannot be developed. This is because harmful components migrate to the salt, which tends to cause chemical fog. Thirdly, in order to prevent deterioration of image quality due to chemical dust etc., the sample containing the radiolabeled substance must be exposed in a dry state while being superimposed on the radiographic film. For this reason, the sample is usually dried or wrapped in a synthetic resin film or the like. If such a clutter occurs in an image obtained by autoradiography, the accuracy of the positional information of the radiolabeled substance will be significantly reduced. For the reasons mentioned above, the operation of autoradiography has become complicated. In addition, the silver salt of the photosensitive component of radiographic film has the disadvantage that it is easily affected not only by scientific stimuli but also by physical stimuli associated with operations such as moving and installing the film, which also makes it difficult to operate autoradiography. This makes it difficult and causes a decrease in accuracy. That is, radiation films tend to cause physical fogging due to physical pressure caused by contact with a sample. In order to avoid such physical fogging of the radiographic film, a high degree of skill and care is required in handling the film, which results in further complicated autoradiography operations. Furthermore, since conventional autoradiography involves long exposure operations as described above,
There is a problem in that natural radioactivity contained in a sample other than the radiolabeled substance is also involved in the exposure of the radiation film, reducing the accuracy of the obtained positional information of the radiolabeled substance. In order to eliminate interference caused by such natural radioactivity, attempts have been made, for example, to conduct parallel experiments using control samples and to optimize the exposure time.
The disadvantage is that the entire operation becomes complicated due to the necessity of preliminary experiments to determine a suitable exposure time. Furthermore, in conventional autoradiography, in order to obtain the necessary information from an imaged autoradiograph, it is necessary to perform the simple task of visually reading the position information over a long period of time. It was necessary. In particular, as mentioned above, it is not easy to obtain positional information about many types of radiolabeled substances from a single radiation film. [Summary of the Invention] The present inventor has discovered that conventional autoradiography,
In particular, as a result of intensive research aimed at solving the above-mentioned problems associated with autoradiography using the double labeling method, we have developed a fluorescent film containing a stimulable phosphor instead of a radiation film as a photosensitive material. By using a stimulable phosphor sheet or a stimulable phosphor sheet laminate having multiple body layers,
It has been discovered that the above problems can be solved or the drawbacks can be reduced, and the present invention has been achieved. That is, the present invention obtains positional information of multiple types of radiolabeled substances contained in a sample selected from the group consisting of biological tissue and a medium containing biological tissue and/or biological material. In an autoradiographic recording method comprising: (1) overlapping the sample and a stimulable phosphor sheet having a plurality of phosphor layers containing a stimulable phosphor for a certain period of time, the radioactivity of the plurality of types is recorded. Depending on the energy level of the radiation emitted from each labeled substance, the phosphor layer closer to the sample preferentially absorbs the radiation from the radiolabeled substance that emits radiation with lower average energy, and A step of causing the phosphor layers on the farther side to preferentially absorb radiation from a radiolabeled substance that emits radiation with higher average energy; (2) irradiating the plurality of phosphor layers of the stimulable phosphor sheet with electromagnetic waves; a step of exciting and emitting the radiation energy stored and recorded in each phosphor layer as photostimulated light, and detecting each of the photostimulated lights to obtain image signals corresponding to each phosphor layer; and (3) obtaining positional information for each of the plurality of radiolabeled substances in the sample by performing subtraction processing between each image signal. This is what we provide. The present invention also provides a stimulable phosphor sheet used in the above-mentioned autoradiographic recording method, that is, a stimulable phosphor sheet having a plurality of phosphor layers made of a binder containing and supporting a stimulable phosphor in a dispersed state. In the body sheet, the layer thickness of the phosphor layer on the surface side of at least one sheet is such that the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S The present invention also provides a stimulable phosphor sheet having a size equal to or slightly larger than . Furthermore, in the above autoradiographic recording method, the present invention provides, in place of the stimulable phosphor sheet having a plurality of phosphor layers containing a stimulable phosphor,
The present invention also provides a method of using a stimulable phosphor sheet laminate having a plurality of stimulable phosphor sheets, and a stimulable phosphor sheet laminate used in the method. In addition, in the present invention, "position information" of a radiolabeled substance contained in a sample refers to various information centered on the position of a radiolabeled substance or an aggregate thereof in a sample, such as information on the radioactivity present in a sample. Refers to various types of information obtained as one or any combination of information such as the location and shape of a material aggregate, the concentration and distribution of radioactive materials at that location, etc. Furthermore, in the present invention, "multiple types of radiolabeled substances" also means the same substance with different labels. [Structure of the Invention] The stimulable phosphor sheet of the present invention is also called a radiation image conversion panel, and examples thereof are described in, for example, Japanese Patent Application Laid-Open No. 12145/1983.
Its general configuration is already known. That is, the stimulable phosphor sheet is made of stimulable phosphor, and the stimulable phosphor of the sheet absorbs the radiation energy that has passed through the subject or the radiation energy that has been emitted from the subject, and then By exciting the sheet using electromagnetic waves (excitation light) in the visible to infrared region, the radiation energy stored in the stimulable phosphor of the sheet can be emitted as fluorescence. Therefore, a subject or a radiation image of the subject is obtained by photoelectrically reading this fluorescence and converting it into an electrical signal, and the obtained electrical signal is reproduced as a visible image on a recording material such as photographic film or a display device such as a CRT. Alternatively, it can be expressed as numerical or symbolic position information. According to the method of the present invention, in autoradiography using a multiple labeling method, a stimulable fluorescent film containing a stimulable phosphor is used instead of a radiation film used in conventional autoradiography. By using a body sheet or a stimulable phosphor sheet laminate, positional information of a sample containing multiple types of radiolabeled substances can be individually obtained.
That is, it is possible to obtain positional information of substances radioactively labeled with different radioisotopes by classifying them for each radioisotope. Furthermore, when a stimulable phosphor sheet is used as a photosensitive material, there is no need for special imaging to obtain positional information of the radiolabeled substance accumulated and recorded on the stimulable phosphor sheet; By scanning the sheet with electromagnetic waves such as a laser, the above positional information can be read out, and the positional information can be converted into an arbitrary form such as an image, symbol and/or numerical value, or a combination thereof. Furthermore, by further processing the above-mentioned position information using electrical means etc., the position information is obtained in various desired forms, that is, the position information is not necessarily obtained in the form of an image, but the image information is processed as data. It is also possible to obtain it as other information that can be obtained. For example, it is also possible to obtain information regarding the target biological system by analyzing, using a computer or the like, an electrical signal or digital signal having positional information of a radiolabeled substance obtained by reading out a stimulable phosphor sheet. Furthermore, according to the method of the present invention, not only is it possible to significantly shorten the exposure time, but also the accuracy of the obtained positional information is improved even when the exposure is performed at or near the ambient temperature. never deteriorates. Therefore, the exposure operation, which was conventionally carried out over a long period of time under cooling, is significantly simplified, and the autoradiography operation is simplified. Furthermore, by using the above-mentioned stimulable phosphor sheet as a photosensitive material used in the autoradiographic recording method, chemical fog and physical fog, which have traditionally been a major problem when using radiation film, are virtually eliminated. This fact is also very advantageous in improving the accuracy of the obtained position information and in terms of workability. In addition, deterioration in accuracy due to radioactivity of impurities contained in the sample or natural radioactivity can be easily reduced by electrically processing the position information stored and recorded on the stimulable phosphor sheet. Or it can be resolved. Next, the stimulable phosphor sheet and stimulable phosphor sheet laminate of the present invention, which can be suitably used in an autoradiographic recording method, will be described in detail with reference to the accompanying drawings. The basic structure of a stimulable phosphor sheet is a support and a phosphor layer provided on one side of the support. However, if the phosphor layer itself is self-supporting, it is not necessarily necessary to provide a support. In addition, a transparent protective film is generally provided on the surface of the phosphor layer (if a support is provided on one side of the phosphor layer, the surface not facing the support), and the phosphor layer protects it from chemical alteration or physical impact. A typical embodiment of the stimulable phosphor sheet of the present invention is as shown in FIG. Note that FIG. 1 is a sectional view showing an embodiment of a stimulable phosphor sheet. (1) A stimulable phosphor sheet [FIG. 1a] consisting of a protective film 1a, a first phosphor layer 2a, a second phosphor layer 3a, and a protective film 4a in this order. (2) A stimulable phosphor sheet [FIG. 1b] consisting of a protective film 1b, a first phosphor layer 2b, a second phosphor layer 3b, and a support 5b in this order. (3) A stimulable phosphor sheet [FIG. 1c] consisting of, in order, a protective film 1c, a first phosphor layer 2c, an intermediate layer 6c, a second phosphor layer 3c, and a protective film 4c. (4) A stimulable phosphor sheet [FIG. 1d] consisting of a protective film 1d, a first phosphor layer 2d, an intermediate layer 6d, a second phosphor layer 3d, and a support 5d. However, the embodiment shown in FIG. 1 is an example of a typical embodiment, and the stimulable phosphor sheet of the present invention is not limited to the above four embodiments. For example, the phosphor layers constituting the stimulable phosphor sheet of the present invention are not limited to two layers, but may be composed of three or more phosphor layers. In addition, when the phosphor layer consists of three or more layers and an intermediate layer is provided, the intermediate layer only needs to be provided at least one place between each phosphor layer, and even if it is provided between each phosphor layer. I don't mind. The above is an example of the stimulable phosphor sheet of the present invention.
(2) The stimulable phosphor layer sheet having the structure shown in FIG. 1b can be manufactured, for example, by the method described below. The phosphor layer is basically a layer consisting of a binder containing and supporting a particulate stimulable phosphor layer in a dispersed state. As mentioned above, a stimulable phosphor is a phosphor that exhibits stimulated luminescence when irradiated with radiation and then with excitation light, but from a practical point of view, it has a wavelength of 400~
300-500nm with excitation light in the 900nm range
It is desirable that the phosphor exhibits stimulated luminescence in the wavelength range of . The stimulable phosphor used in the stimulable phosphor sheet used in the present invention is preferably a divalent europium-activated alkaline earth metal fluorohalide phosphor, but is not limited thereto. isn't it. Examples of stimulable phosphors used in the stimulable phosphor sheet used in the present invention include those described in U.S. Pat. No. 3,859,527.
SrS: Ce, Sm, SrS: Eu, Sm, ThO ₂ : Er, and La ₂ O ₂ S: Eu, Sm, described in JP-A-55-12142.
ZnS: Cu, Pb, BaO・xAl ₂ O ₃ : Eu (however, 0.8
≦x≦10) and M〓O・xSiO ₂ :A (however,
M〓 is Mg, Ca, Sr, Zn, Cd, or Ba,
A is Ce, Tb, Eu, Tm, Pb, Tl, Bi, or
(Ba _1-xy , Mg _x , Ca _y ) FX: aEu ²⁺ (where X
is at least one of Cl and Br,
x and y are 0<x+y≦0.6 and xy≠0, and a is ^10-6 ≦a≦5× ^10-2 ), as described in JP-A-55-12144.
LnOX:xA (Ln is La, Y, Gd, and
At least one of Lu, X is at least one of Cl and Br, A is at least one of Ce and Tb, and x is 0<x<0.1
(Ba _1-X , M ²⁺ _X )FX:yA (where M ²⁺ is Mg,
At least one of Ca, Sr, Zn, and Cd, X is at least one of Cl, Br, and I, A is Eu, Tb, Ce, Tm, Dy, Pr, Ho,
at least one of Nd, Yb, and Er, x is 0x≦0.6, and y is 0≦y≦0.2), M〓 described in JP-A-55-160078.
FX・xA: yLn [However, M〓 is Ba, Ca, Sr,
At least one of Mg, Zn, and Cd, A
are BeO, MgO, CaO, SrO, BaO, ZnO,
Al ₂ O ₃ , Y ₂ O ₃ , La ₂ O ₃ , In ₂ O ₃ , SiO ₂ , TlO ₂ ,
ZrO ₂ , GeO ₂ , SnO ₂ , Nb ₂ O ₅ , Ta ₂ O ₅ , and
At least one of ThO ₂ , Ln is Eu, Tb,
Ce, Tm, Dy, Pr, Ho, Nd, Yb, Er, Sm,
and at least one of Gd, X is Cl,
At least one of Br, and I,
x and y are respectively 5×10 ^-5 ≦x≦0.5 and 0<y≦0.2] A phosphor is described in JP-A-56-116777 (Ba _{1- X , M〓 _}
M〓 is beryllium, magnesium, calcium,
at least one of strontium, zinc, and cadmium; X is at least one of chlorine, bromine, and iodine; A is at least one of zirconium and scandium;
a, x, y, and z are each 0.5≦a≦1.25,
0≦x≦1, 10 ^-6 ≦y≦2×10 ^-1 , and 0<z
≦10 ^-2 ] _, described in Japanese Patent Application Laid-open No. 57-23673 (Ba _{1 -X ,} M〓 ,
M〓 is beryllium, magnesium, calcium,
at least one of strontium, zinc, and cadmium;
10 ^-6 ≦y≦2×10 ^-1 and 0<z≦2×10 ^-1 ] A phosphor is described in JP-A-57-23675 (Ba _{1 -X , M〓 _}
M〓 is at least one of beryum, magnesium, calcium, strontium, zinc, and cadmium, X is at least one of chlorine, bromine, and iodine, A is at least one of arsenic and silicon, a, x, y and z
are respectively 0.5≦a≦1.25, 0≦x≦1, 10 ^-6 ≦y
≦2×10 ^-1 and 0<z≦5×10 ^-1 ], M〓 described in JP-A-58-69281
OX: xCe [However, M〓 is Pr, Nd, Pm, Sm,
At least one trivalent metal selected from the group consisting of Eu, Tb, Dy, Ho, Er, Tm, Yb, and Bi, X is one or both of Cl and Br, and x is 0<x<0.1] A phosphor is described in JP-A-58-206678.
Ba _1-X M _X/2 L _X-2 FX: yEu ²⁺ [However, M is Li,
represents at least one alkali metal selected from the group consisting of Na, K, Rb, and Cs; L is
Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Gd,
Tb, Dy, Ho, Er, Tm, Yb, Lu, Al, Ga,
represents at least one type of trivalent metal selected from the group consisting of In, and Tl; X represents at least one type of halogen selected from the group consisting of Cl, Br, and I; and x represents 10 ^-2 ≦ x ≦0.5,
y is 0<y≦0.1] A phosphor is described in JP-A-59-27980.
BaFX・xA:yEu ²⁺ [wherein, 10 ^-6 ≦x≦
0.1, y is 0<y≦0.1], which is described in Japanese Patent Application Laid-open No. 59-47289.
BaFX・xA:yEu ²⁺ [However, X is at least one halogen selected from the group consisting of Cl, Br, and I; A is hexafluorosilicic acid,
x is a fired product of at least one compound selected from the hexafluoro compound group consisting of monovalent or divalent metal salts of hexafluorotitanic acid and hexafluorozirconic acid;
10 ^-6 ≦x≦0.1, y is 0<y≦0.1] A phosphor described in JP-A No. 59-56479
BaFX・xNaX′; aEu ²⁺ [However, X and X′ are
Each is at least one of Cl, Br, and I, and x and a are each 0<x≦2,
and 0<a≦0.2], M〓 described in JP-A No. 59-56480
FX・xNaX′: yEu ²⁺ : zA [However, M〓 is Ba,
at least one alkaline earth metal selected from the group consisting of Sr, and Ca;
X′ is at least one kind of halogen selected from the group consisting of Cl, Br, and I;
is at least one transition metal selected from V, Cr, Mn, Fe, Co, and Ni; and
A phosphor ^represented by the composition formula: There M〓
FX・aM〓X′・bM′〓X″ ₂ .cM〓X ₃・xA：yEu ²⁺
[However, M〓 is at least one kind of alkaline earth metal selected from the group consisting of Ba, Sr, and Ca; M〓 is at least one kind selected from the group consisting of Li, Na, K, Rb, and Cs. is an alkali metal; M′〓 is at least one divalent metal selected from the group consisting of Be and Mg; M〓 is
At least one trivalent metal selected from the group consisting of Al, Ga, In, and Tl; A is a metal oxide; X is at least one halogen selected from the group consisting of Cl, Br, and I; can be;
X′, X″, and X are F, Cl, Br, and I
at least one kind of halogen selected from the group consisting of; and a is 0≦a≦2, and b is 0≦b
≦10 ^-2 , c is 0≦0≦10 ^-2 , and a+b+c≧
10 ^-6 ; x is 0<x≦0.5, y is 0<y≦0.2
A phosphor represented by the composition formula of
X ₂・aM〓X′ ₂ :xEu ²⁺ [However, M〓 is at least one alkaline earth metal selected from the group consisting of Ba, Sr, and Ca;
and I, and X≠X'; and a is 0.1≦a≦10.0, and x is 0<x≦0.2]
A phosphor represented by the composition formula M〓FX・aM〓X′:xEu ²⁺ [However,
M〓 is at least one kind of alkaline earth metal selected from the group consisting of Ba, Sr and Ca; M〓
is at least one kind of alkali metal selected from the group consisting of Rb and Cs; X is at least one kind of halogen selected from the group consisting of Cl, Br and I; X′ consists of F, Cl, Br and I at least one halogen selected from the group; and a and x are 0≦a≦4.0 and 0<x≦0.2, respectively], a phosphor represented by the composition formula: M〓X:xBi [where M ¹ is at least one alkali metal selected from the group consisting of Rb and Cs; X is at least one selected from the group consisting of Cl, Br, and I A phosphor is a type of halogen; and x is a numerical value in the range of 0<x≦0.2]. In addition, the M〓X ₂・aM〓X′ ₂ :xEu ²⁺ phosphor described in the above-mentioned Japanese Patent Application Laid-Open No. 60-84381 contains the following additives as M〓X ₂・aMX′ ₂ May be contained in the following proportions per mole. bM〓X″ (where M〓 is Rb and Cs
X″ is at least one halogen selected from the group consisting of F, Cl, Br and I, and b satisfies 0<b≦10.0); Gansho 59
−bKX″/cMgX described in specification No. 77225
₂・dM〓X′′′′′ ₃ (However, M〓 is Sc, Y, La, Gd
and at least one kind of trivalent metal selected from the group consisting of Lu, and X'', and b, c and d are 0≦b≦2.0, 0≦
c≦2.0, 0≦d≦2.0, and 2×10 ^-5 ≦
b+c+d); yB described in the specification of Japanese Patent Application No. 59-84356 (however, y is 2×10 ^-4 ≦y≦
2×10 ^-1 ); bA described in Japanese Patent Application No. 1984-84358 (where A is SiO ₂ and P ₂ O ₅
bSiO as described in Japanese Patent Application No. ^59-240452 (however, bSiO is at least one kind of oxide selected from the group consisting ^of bSnX″ ² described in the specification of Japanese Patent Application No. 59-240454 (where X″ is selected from the group consisting of _F , Cl, Br and I); and b is 0<b≦10 ^-3 ); bCsX″・cSnX ₂ (where X″ and X
are at least one kind of halogen selected from the group consisting of F, Cl, Br and I, and b and c are respectively 0<b≦10.0 and
^10-6 ≦c≦2× ^10-2 )
bCsX″・yLn ³⁺ (However, X″ is at least one kind of halogen selected from the group consisting of F, Cl, Br, and I, and Ln is Sc, Y, Ce, Pr, Nd, Sm,
At least one rare earth element selected from the group consisting of Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu, and b and y are each 0<b≦
10.0 and 10 ^-6 ≦y≦1.8×10 ^-1 ). etc. can be mentioned. However, the stimulable phosphor used in the present invention is not limited to the above-mentioned phosphors, but any phosphor that exhibits stimulated luminescence when irradiated with radiation and then irradiated with excitation light. It may be. Examples of binders for the phosphor layer include proteins such as gelatin, polysaccharides such as dextran, or natural polymeric substances such as gum arabic; and polyvinyl butyral, polyvinyl acetate, nitrocellulose, ethylcellulose, and vinylidene chloride. Binders represented by synthetic polymeric substances such as vinyl chloride copolymers, polyalkyl (meth)acrylates, vinyl chloride/vinyl acetate copolymers, polyurethanes, cellulose acetate butyrate, polyvinyl alcohol, linear polyesters, etc. can. Particularly preferred among such binders are nitrocellulose, linear polyesters, polyalkyl(meth)
acrylates, mixtures of nitrocellulose and linear polyesters and mixtures of nitrocellulose and polyalkyl (meth)acrylates.
Note that these binders may be crosslinked with a crosslinking agent. The phosphor layer can be formed on the support, for example, by the following method. Examples of binders for the phosphor layer include proteins such as gelatin, polysaccharides such as dextran, or natural polymeric substances such as gum arabic; and polyvinyl butyral, polyvinyl acetate, nitrocellulose, ethylcellulose, chloride Binders typified by synthetic polymeric materials such as vinylidene/vinyl chloride copolymers, polyalkyl (meth)acrylates, vinyl chloride/vinyl acetate copolymers, polyurethanes, cellulose acetate butyrate, polyvinyl alcohol, linear polyesters, etc. I can do it. Particularly preferred among such binders are nitrocellulose, linear polyesters, polyalkyl (meth)acrylates, mixtures of nitrocellulose and linear polyesters, and mixtures of nitrocellulose and polyalkyl (meth)acrylates. It is. The second phosphor layer can be formed on the support, for example, by the following method. First, a particulate stimulable phosphor and a binder are added to a suitable solvent and thoroughly mixed to prepare a coating solution in which the stimulable phosphor is uniformly dispersed in the binder solution. Examples of solvents for preparing coating solutions include lower alcohols such as methanol, ethanol, n-propanol, and n-butanol; chlorine-containing hydrocarbons such as methylene chloride and ethylene chloride; and ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone. ; esters of lower fatty acids and lower alcohols such as methyl acetate, ethyl acetate, and butyl acetate; ethers such as dioxane, ethylene glycol monoethyl ether, and ethylene glycol monomethyl ether; and mixtures thereof. The mixing ratio of the binder and the stimulable phosphor in the coating solution varies depending on the characteristics of the desired stimulable phosphor sheet, the type of phosphor, etc., but in general, the mixing ratio of the binder and the stimulable phosphor is is selected from the range of 1:1 to 1:100 (weight ratio), and especially 1:8 to 1:100 (weight ratio).
It is preferable to select from a range of 140 (weight ratio). The coating liquid also contains a dispersant to improve the dispersibility of the phosphor in the coating liquid, and a dispersant to improve the bonding force between the binder and the phosphor in the phosphor layer after formation. Various additives such as plasticizers may be mixed. Examples of dispersants used for such purposes include phthalic acid, stearic acid, caproic acid, lipophilic surfactants, and the like. Examples of plasticizers include phosphoric acid esters such as triphenyl phosphate, tricresyl phosphate, and diphenyl phosphate; phthalic acid esters such as diethyl phthalate and dimethoxyethyl phthalate; and ethyl phthalyl ethyl glycolate and butyl phthalyl butyl glycolate. Glycolic acid esters; and polyesters of polyethylene glycol and aliphatic dibasic acids, such as polyesters of triethylene glycol and adipic acid and polyesters of dimethylene glycol and succinic acid. The coating solution containing the phosphor and binder prepared as described above is then uniformly applied to the surface of the support to form a coating film of the coating solution.
This coating operation can be carried out using conventional coating means such as a doctor blade, roll coater, knife coater, etc. The support may be arbitrarily selected from various materials used as supports for intensifying screens (or intensifying screens) in conventional radiography or materials known as supports for stimulable phosphor sheets. I can do it. Examples of such materials include:
Cellulose acetate, polyester, polyethylene terephthalate, polyamide, polyimide,
Films of plastic materials such as triacetate and polycarbonate, metal sheets such as aluminum foil and aluminum alloy foil, regular paper, baryta paper, resin coated paper, pigment paper that also contains pigments such as titanium dioxide, paper sized with polyvinyl alcohol, etc. etc. can be mentioned. However, in consideration of the characteristics and handling of the stimulable phosphor sheet as an information recording material, the preferred material for the support in the present invention is plastic film. This plastic film may be kneaded with a light-absorbing substance such as carbon black, or may be kneaded with a light-reflecting substance such as titanium dioxide. The former is a support suitable for a high sharpness type stimulable phosphor sheet, and the latter is a support suitable for a high sensitivity type stimulable phosphor sheet. In known stimulable phosphor sheets, in order to strengthen the bond between the support and the phosphor layer, or to improve the sensitivity or image quality of the stimulable phosphor sheet, the surface of the support on the side where the phosphor layer is provided is A polymeric substance such as gelatin is coated on the surface to form an adhesion-imparting layer, or a light-reflecting layer made of a light-reflecting substance such as titanium dioxide or a light-absorbing layer made of a light-absorbing substance such as carbon black is provided. is also being carried out. The support used in the present invention can also be provided with these various layers. Furthermore, as disclosed in JP-A No. 58-200200, in order to improve the sharpness of the obtained image, the surface of the support on the phosphor layer side (the surface of the support on the phosphor layer side) When an adhesion-imparting layer, a light-reflecting layer, a light-absorbing layer, a metal foil, or the like is provided, the surface (meaning the surface thereof) may have irregularities. However, if the stimulable phosphor sheet is to be read out from the surface of the support as described later, the support is preferably a transparent plastic film with a flat surface, and the phosphor layer is formed on this support. Preferably, it is provided directly on top. Then, the formed coating film is dried by gradually heating it to complete the formation of the second phosphor layer on the support. The thickness of the phosphor layer varies depending on the characteristics of the desired stimulable phosphor sheet, the type of phosphor particles, the mixing ratio of the binder and the phosphor particles, etc., but usually
The thickness should be 5 μm to 1 mm. However, the thickness of this layer is preferably 10 to 500 μm. Note that the second phosphor layer does not necessarily need to be formed by directly applying a coating liquid onto the support as described above; After forming a phosphor layer by coating and drying, the phosphor layer may be pressed onto a support, or the support and phosphor layer may be bonded by a method using an adhesive. Next, a first phosphor layer is formed on the second phosphor layer. This first phosphor layer can be formed in the same manner as the second phosphor layer using a material that can be used in forming the second phosphor layer.
The second phosphor layer and the first phosphor layer can be formed by coating them separately or sequentially, or by coating and drying them simultaneously. However, when providing the first phosphor layer directly on the second phosphor layer, the binder used in the first phosphor layer and Preferably, the solvent is different from that of the second phosphor layer. Note that the stimulable phosphor used in the first phosphor layer may be the same as the phosphor in the second phosphor layer, but it is preferable that the stimulable phosphor used in the first phosphor layer be a different phosphor whose main emission wavelengths do not overlap. preferable. In particular, when the radiation energy absorbed and stored in the first and second phosphor layers is simultaneously read out from one side of the sheet, it is necessary to use different phosphors with nonoverlapping emission wavelengths. In addition, in order to more efficiently absorb and store radiation from radioactive elements with low average energy in the first phosphor layer placed on the sample side when using a stimulable phosphor sheet, it is necessary to Preferably, the exhaustible phosphor has high absorption characteristics for low-energy radiation. In addition, in order to further enhance the shielding effect against low-energy radiation in the first phosphor layer,
For example, metals (Cu, W, Mo,
A low energy absorbing substance such as Ni, Pb, etc.) may be included. Next, a protective film is provided on the first phosphor layer. This protective film may be formed, for example, by bonding a transparent thin film separately formed from polyethylene terephthalate, polyethylene, vinylidene chloride, polyamide, etc. to the surface of the first phosphor layer using a suitable adhesive. I can do it. Alternatively, the protective film may be a transparent polymer such as a cellulose derivative such as cellulose acetate or nitrocellulose; or a synthetic polymer material such as polymethyl methacrylate, polyvinyl butyral, polyvinyl formal, polycarbonate, polyvinyl acetate, or vinyl chloride/vinyl acetate copolymer. It can also be formed by a method in which a solution prepared by dissolving a substance in a suitable solvent is applied to the surface of the first phosphor layer. The thickness of the transparent protective film formed in this way is usually approximately
It is desirable that the thickness be 0.1 to 50 μm, preferably 0.3 to 20 μm. The stimulable phosphor sheet produced in this manner is described in Japanese Patent Application Laid-open No. 55-163500 and Japanese Patent Application No. 171545 filed by the present applicant. At least a portion of the sheet may be colored with a suitable coloring agent for the purpose of increasing the sharpness of the sheet. When an intermediate layer is provided between the phosphor layers as shown in FIG. This can be done by coating on the phosphor layer. Alternatively, in a stimulable phosphor sheet having the structure as shown in FIG. 1c, the intermediate layer may be made of a material used for the support so that it also serves as the support. In the present invention, the intermediate layer is provided to provide a shielding effect by absorbing radiation from radioactive elements with low average energy. In other words, radiation from radioactive elements with low average energy is absorbed only by the phosphor layer on the sample side with the intermediate layer as a boundary, and acts as a barrier to prevent it from being absorbed by the phosphor layer on the opposite side. It is. The above effect can be achieved by making the thickness including the intermediate layer from the surface of the sheet on the sample side equal to the maximum range of radiation from the target radioactive element. Therefore, the thickness of the intermediate layer varies depending on the characteristics of the intended stimulable phosphor sheet, the thickness of the phosphor layer, the material of the intermediate layer, etc., but is generally 1 to 500 μm.
shall be. However, the thickness of this layer is preferably 3 to 200 μm. Further, it is preferable that the material used for the intermediate layer has a high density. This intermediate layer is, for example, Cu, W, Mo, Ni, Pb.
The absorption characteristics for low-energy radiation may be enhanced by containing metals such as. Furthermore, if the intermediate layer reads out each phosphor layer of the stimulable phosphor sheet from both sides of the sheet as described above, the stimulated luminescence from the phosphor layers below the intermediate layer can also be read out at the same time. The phosphor layer may be colored with a coloring agent that absorbs light in the emission wavelength range of the stimulable phosphor contained in the phosphor layer. The layer structure and the layer thickness of each layer, which are characteristic requirements of the stimulable phosphor sheet of the present invention that can be manufactured as described above, are based on the type and content of radioisotopes contained in the sample and the amount of emitted radioisotopes. It is suitably selected depending on the intensity of the radiation. Examples of radioisotopes used to radiolabel samples include ^3H , ^125I , ^14C , 35S,
Can list 32P. For example, when a sample contains two types of radioactive elements, the radiation from the radioactive elements that emit radiation with relatively low average energy is absorbed by the phosphor layer on the sample side (in the configuration shown in Figure 1b, the first The layer thickness of the first phosphor layer must be adjusted in order to cause radiation from the other radioactive element to be mainly absorbed by the phosphor layer (also the second phosphor layer) on the side far from the sample. be greater than or equal to the maximum range of the former low-energy radiation and smaller than the maximum range of the latter high-energy radiation. In order to more efficiently divide and absorb radiation energy into separate phosphor layers for each radioactive element, that is, depending on the level of energy of the emitted radiation, the first phosphor layer differs depending on the combination of radioactive elements. It is desirable that the thickness of the body layer be equal to or slightly larger than the maximum range of radiation from radioactive elements that emit low-energy radiation. Radiation emitted from the above radioisotopes (β
The maximum range of ¹²⁵ I (X-rays only) in the phosphor layer is about the values shown in Table 1, although it varies depending on the material used for the phosphor layer. Therefore, the layer thickness of the phosphor layer on the sample side is the first
Particularly preferred is the range shown in the table.

[Table] One phosphor layer may have the above layer thickness, or the sum of multiple layers may have the above layer thickness. Further, when a protective film, an intermediate layer, etc. are provided, the total thickness including those layers should be the above-mentioned layer thickness. for example,
If the radioactive isotopes contained in the sample are ³ H and ¹⁴ C, and the stimulable phosphor sheet has the configuration shown in Figure 1b, the thickness of the protective film should be 0.3 to 1 μm.
It is preferable that the thickness of the first phosphor layer is 10 to 15 μm, and the thickness of the second phosphor layer is 100 to 250 μm.
For example, if the radioactive element contained in the sample is ¹⁴ C
and ³² P, and when the stimulable phosphor sheet has the configuration shown in Figure 1 d, the thickness of the protective film is 0.5 to 10 μm, and the thickness of the first phosphor layer is 100 to 150 μm.
m, the thickness of the intermediate layer is 50 to 200 μm, and the protective film is
The total thickness of the first phosphor layer and intermediate layer is 200~
The layer thickness of the second phosphor layer was set to 300 μm.
It is preferable to set it as 100-300 micrometers. The type of stimulable phosphor contained in each phosphor layer,
It is desirable to select the mixing ratio appropriately depending on the type and combination of target radioactive elements, their radiation intensity, etc., and it is also related to the layer structure and layer thickness of the stimulable phosphor sheet as described above. be selected as appropriate. Further, as a typical embodiment of the stimulable phosphor sheet laminate of the present invention, an embodiment as shown in FIG. 2 can be mentioned. Note that FIG. 2 is a sectional view showing an embodiment of the stimulable phosphor sheet laminate of the present invention. (1) A first stimulable phosphor sheet a (protective film 1a, phosphor layer 2a, support 3a) and a second stimulable phosphor sheet b (protective film 1b, phosphor layer 2b, support 3b). [Fig. 1] (2) First stimulable phosphor sheet a (protective film 1a, phosphor layer 2a, support 3a), barrier c, and second stimulable phosphor sheet b (protective film 1a, phosphor layer 2a, support 3a) A sheet laminate consisting of a film 1b, a phosphor layer 2b, and a support 3b [Fig. 1 2] However, the two embodiments shown in Fig. 2 are examples of typical embodiments, and the present invention The stimulable phosphor sheet laminate is not limited to the above two types of embodiments. For example, the number of stimulable phosphor sheets constituting the stimulable phosphor sheet laminate of the present invention is not limited to two, but may be composed of three or more stimulable phosphor sheets. In addition, when the stimulable phosphor sheets are composed of three or more sheets and a barrier is provided between them, the barrier may be provided at least at one location between each sheet,
It may be provided between each sheet. The stimulable phosphor sheet can be manufactured in the same manner as described above. The sheet used in the stimulable phosphor sheet laminate may have a single phosphor layer, or may have a layered structure including a plurality of phosphor layers as described above. The barrier can also be chosen, for example, from among the materials used for the supports mentioned above. The barrier may contain dispersed low energy absorbing materials such as the metals mentioned above. In the stimulable phosphor sheet laminate shown in FIG. Absorbent substances may also be included. The thickness of each stimulable phosphor sheet, which is a characteristic requirement of the present invention, is preferably within the range shown as the layer thickness of the phosphor layer in Table 1 above.
Further, a plurality of stimulable phosphor sheets may have the above thickness, and if a barrier is further provided, the total thickness including the barrier may be the above thickness. Then, a stimulable phosphor sheet (or stimulable phosphor sheet and barrier, hereinafter the same) for mainly absorbing radiation from radioactive isotopes that emit radiation with low average energy is placed on the outside, and radiation with higher average energy is placed on the outside. The stimulable phosphor sheet laminate of the present invention is prepared by sequentially laminating stimulable phosphor sheets for mainly absorbing radiation from a radioactive isotope that emits . Next, the autoradiograph recording method of the present invention will be explained. The autoradiographic recording method of the present invention uses the stimulable phosphor sheet (or stimulable phosphor sheet laminate) of the present invention having the above-described configuration.
This can be preferably carried out by using. That is, the autoradiographic recording method of the present invention uses the above-mentioned stimulable phosphor sheet in place of a conventional photosensitive material consisting of a radiation film, and the exposure operation involves the use of a sample containing a radiolabeled substance and a stimulable phosphor sheet. This is carried out by overlapping the sheet with a radioactive phosphor sheet for a certain period of time, so that at least a portion of the radiation emitted from the radiolabeled substance of the sample is absorbed by the sheet. In the present invention, the sample to be recorded by autoradiography is a sample selected from the group consisting of biological tissue and a medium containing biological tissue and/or biological material. Here, the medium containing biological tissues and/or biologically derived substances includes, for example, a support medium in which biopolymer substances such as proteins, acids, derivatives thereof, and decomposition products thereof have been separated and developed. can be mentioned. Furthermore, the radiolabeled substance contained in the sample can be obtained by allowing the sample to be recorded or a specific substance in the sample to retain a radioactive isotope in an appropriate manner. The radioactive isotope used in the present invention includes radiation (α rays, β rays, γ rays, neutron rays,
Any species may be used as long as it emits radiation (rays, etc.), but representative examples include the above-mentioned species.
Examples include ³ H, ¹²⁵ I, ¹⁴ C, ³⁵ S, and ³² P. A sample to be recorded according to the present invention has many kinds of radiolabeled substances radiolabeled with at least two different kinds of radioactive elements. In the exposure operation, the above-mentioned sample is superimposed on a stimulable phosphor sheet either as it is or after any treatment such as drying or fixation of the separated developable material, so that the autoradiograph of the sample is Accumulated and recorded on the phosphor sheet. The overlapping state of the sample and the stimulable phosphor sheet is usually achieved by bringing the sample and the stimulable phosphor sheet into close contact with each other, but it is not necessary that they come into close contact with each other, and it is possible to place them in close proximity. may have been done. Note that in the stimulable phosphor sheet of the present invention, which is composed of multiple phosphor layers, this superposition is such that the phosphor layer for absorbing and accumulating lower energy radiation is placed on the sample side. It is done. For example, in the stimulable phosphor sheets shown in FIGS. 1a to 1d, the protective films 1a to 1d are arranged on the sample side. In addition, in the stimulable phosphor sheet laminate of the present invention, which is composed of a plurality of stimulable phosphor sheets, the sheets are stacked so that the stimulable phosphor sheet for absorbing and accumulating lower energy radiation is on the sample side. It is done by positioning the body.
For example, in the stimulable phosphor sheet laminate shown in FIGS. 1 and 2, the stimulable phosphor sheet a is placed on the sample side. Barrier c as shown in Fig. 2
When using a sheet laminate having a stimulable phosphor sheet and the sample does not show a significant change over time, first stack the stimulable phosphor sheet a and the sample and expose them to light, then sandwich the barrier c between them. By overlapping the stimulable phosphor sheet b and the sample and exposing them to light, it is also possible to sequentially absorb and accumulate radiation from radioactive isotopes with different energy intensities in different stimulable phosphor sheets. In addition, the so-called exposure time depends on the type of radioisotope contained in the sample, its radiation intensity; the concentration and density of the radiolabeled substance; the sensitivity of the stimulable phosphor sheet, and the positional relationship between the sample and the stimulable phosphor sheet. Although it varies, the exposure operation requires a certain period of time, for example, several seconds or more. However, when the stimulable phosphor sheet of the present invention is used, the exposure time is significantly shortened compared to the exposure time required when using a conventional radiation film. In addition, in the operation of reading out an autoradiograph containing positional information of a radiolabeled substance in a sample accumulated and recorded on a stimulable phosphor sheet from a sample by exposure, the intensity and distribution of the radiation energy absorbed and accumulated on the sheet are determined. It is possible to change the form of position information obtained by applying various electrical processes depending on the state, desired information, etc.
There is no particular need to strictly control the exposure time during the exposure operation. There is no particular restriction on the temperature at which the exposure operation is performed, but
Autoradiography using the stimulable phosphor sheet of the present invention can be carried out at ambient temperatures, particularly from 10 to 35°C. However, the exposure operation may be performed at a low temperature (for example, around 5° C. or lower) that is used in conventional autoradiography. By the above exposure operation, when the stimulable phosphor sheet of the present invention consisting of multiple phosphor layers of the present invention is used as a photosensitive material, radiation from a radioactive element with lower average energy is directed to the phosphor layer on the sample side. The radiation from the radioactive element with higher average energy is absorbed by the phosphor layer on the side farther from the sample, so that the radiation energy is absorbed and stored in a separate phosphor layer for each radiolabeled substance. . However, in the present invention, for example, when there are two types of radioactive elements, by using a stimulable phosphor sheet having the above configuration, the radiation from the radioactive elements that emit radiation with low average energy can be transmitted to the sample. Almost completely absorbed by the side phosphor layer. That is, at least radioactive elements with low average energy can be separated using a plurality of phosphor layers. Therefore, even if the radiation from the other radioactive element with high average energy is absorbed across multiple phosphor layers without being efficiently separated, readout is performed for each phosphor layer as described later, and the fluorescence By performing suitable signal processing such as subtraction on the digital signals obtained for each body layer, position information can be obtained for each radioactive element. Furthermore, when a stimulable phosphor sheet laminate consisting of a plurality of stimulable phosphor sheets of the present invention is used as a photosensitive material, in the same manner, each radiolabeled substance is placed on a separate stimulable phosphor sheet. Allows energy to be absorbed and stored. Below, an example of the reading device (or reading device) shown in FIG. 3 will be described with regard to the method for reading the positional information of the radiolabeled substance indicated by the autoradiograph accumulated and recorded on the stimulable phosphor sheet in the present invention. A brief description will be given with reference to the following. To read out a stimulable phosphor sheet having two phosphor layers (see FIG. 1), which is an example of the stimulable phosphor sheet of the present invention, first, for example, one sheet surface (FIG. 1 a to d) is read out. The positional information accumulated and recorded in the first phosphor layer is read out from the surface of the protective films 1a to 1d). FIG. 3 is a pre-reading screen for tentatively reading out one-dimensional or two-dimensional positional information of a radiolabeled substance accumulated and recorded on a stimulable phosphor sheet (hereinafter sometimes abbreviated as sheet) 1. A schematic diagram of an example of a reading device comprising a reading section 2 and a main reading reading section 3 having a function of reading out an autoradiograph stored and recorded on a sheet 1 in order to output position information of a radiolabeled substance. ing. In the prefetch reading unit 2, the following prefetch operation is performed. The laser light 5 generated from the laser light source 4 passes through the filter 6 to filter out a portion of the wavelength chain corresponding to the wavelength region of stimulated luminescence generated from the stimulable phosphor sheet 1 in response to excitation by the laser light 5. is cut. Then the laser light
After being deflected by a light deflector 7 such as a galvano mirror and reflected by a flat reflector 8, the sheet 1
It is deflected one-dimensionally and incident on the top. The laser light source 4 used here is selected so that the wavelength range of its laser light 5 does not overlap with the main wavelength range of stimulated luminescence emitted from the sheet 1. The stimulable phosphor sheet 1 is transported in the direction of the arrow 9 with the protective films 1a to 1d facing upward while being irradiated with the polarized laser beam 5. Therefore, the entire surface of the sheet 1 is irradiated with the polarized laser beam. Note that the output of the laser light source 4, the beam diameter of the laser light 5, the scanning speed of the laser light 5,
The transport speed of the sheet 1 is adjusted so that the energy of the laser beam 5 for the pre-reading operation is smaller than the energy used for the main reading operation. When the stimulable phosphor sheet 1 is irradiated with the laser light as described above, it exhibits stimulated luminescence with an amount of light proportional to the radiation energy accumulated in the first phosphor layer on the protective film side. is incident on the pre-reading light guide 10. The light guide 10 has a linear entrance surface and is placed close to the scanning line on the stimulable phosphor sheet 1, and has an exit surface that forms a ring to allow light such as photoprints to pass through. It communicates with the light receiving surface of the detector 11. This light guide 1
0 is made by processing a transparent thermoplastic resin sheet such as acrylic synthetic resin, and is constructed so that the light incident from the incident surface is totally reflected inside and transmitted to the exit surface. ing. Stimulated luminescence from the stimulable phosphor sheet 1 is guided through the light guide 10 and reaches the exit surface.
The light is emitted from the exit surface and received by the photodetector 11. The preferable shape, material, etc. of the light guide are disclosed in Japanese Patent Laid-Open Nos. 55-87970 and 56-11397. A filter is attached to the light-receiving surface of the photodetector 11, which transmits only light in the stimulated emission wavelength range and cuts out light in the excitation light (laser light) wavelength range.
It is designed to detect only stimulated luminescence. Stimulated luminescence detected by the photodetector 11 is converted into an electrical signal, which is further amplified by the amplifier 12 and output. The accumulated recording information output from the amplifier 12 is input to the control circuit 13 of the main reading reading section 3. The control circuit 13 operates according to the obtained accumulated recording information so that an image with the most uniform density and contrast and excellent observation and interpretation performance is obtained.
The amplification factor setting value a, the recording scale factor b, and the reproduction image processing condition setting value c are output. The stimulable phosphor sheet 1 for which the pre-reading operation has been completed as described above is transferred to the reading section 3 for main reading. In the main reading reading section 3, the following main reading operation is performed. The laser beam 15 emitted from the main reading laser light source 14 passes through a filter 16 having the same function as the filter 6 described above, and then the beam
The beam diameter is precisely adjusted by the expander 17. Next, the laser beam is deflected by a light deflector 18 such as a galvano mirror, reflected by a plane reflecting mirror 19, and then one-dimensionally deflected and incident on the stimulable phosphor sheet 1. Note that there is a gap of fθ between the optical deflector 18 and the plane reflecting mirror 19.
A lens 20 is arranged to maintain a uniform beam velocity at all times when the polarized laser beam is operated over the sheet 1. The stimulable phosphor sheet 1 is transported in the direction of the arrow 21 with the protective film side facing up, as in the case of the pre-reading operation, under irradiation with the above-mentioned polarized laser beam. Therefore, the entire surface of the sheet 1 is irradiated with the polarized laser beam, as in the pre-reading operation. When the stimulable phosphor sheet 1 is irradiated with laser light as described above, it emits stimulated luminescence with an amount of light proportional to the accumulated radiation energy, as in the pre-reading operation, and this light is used for main reading. The light enters the light guide 22. The main reading light guide 22 has the same material and structure as the pre-reading light guide 10, and the stimulated luminescence guided through the interior of the main reading light guide 22 through repeated total reflection is emitted from its exit surface. Then, the light is received by the photodetector 23. Note that a filter that selectively transmits only the wavelength region of stimulated luminescence is attached to the light receiving surface of the photodetector 23, so that the photodetector 23 detects only stimulated luminescence. The stimulated luminescence detected by the photodetector 23 is converted into an electrical signal, which is amplified to an appropriate level electrical signal in the amplifier 24 whose sensitivity is set according to the amplification factor setting value a, and then A/D converted. The signal is input to the device 25. The A/D converter 25 converts the digital signal into a digital signal using a scale factor suitable for the signal fluctuation range according to the recorded scale factor setting value b, and inputs the digital signal to the signal processing circuit 26 . In addition, by performing the same operation as described above on the other sheet surface of the stimulable phosphor sheet (the surface of the protective films 4a, 4c or the supports 5b, 5d in FIGS. 1 a to d), a second The position information stored in the phosphor layer is read out and input to the signal processing circuit 26. However, it must be noted that the position information obtained in this case is a mirror image of the above-mentioned position information that has already been obtained. In the signal processing circuit 26, first, the position information (image signal) obtained by reading out the plurality of phosphor layers is temporarily stored in a memory (that is, a buffer memory or a non-luminescent memory such as a magnetic disk). , performs subtraction processing on the digital signal. That is, by performing subtraction between corresponding positions in the radiographic image to be subtracted, positional information regarding the radiolabeled substance can be separated for each radioactive element. The subtraction magnification in subtraction processing can be determined by calculating from the thickness of the phosphor layer and the radiation energy, or by simultaneously exposing a reference material and using it as a reference. . After multiplying the image signal by this determined magnification, subtraction is performed between the signals. Regarding the method of subtraction processing of radiographic images, for example, see the patent application filed in 1983 by the present applicant.
-45475 specification in detail. Next, signal processing is performed on each of the obtained positional information based on the reproduction image processing condition setting value c so that a visible image with appropriate density and contrast and excellent observation and interpretation performance is obtained, and then a magnetic tape, etc. The data is transmitted to a recording device (not shown) via storage means. Examples of recording devices include those that scan and record photosensitive materials with laser beams, those that display electronically on CRTs, etc., and those that optically record radiation images displayed on CRTs, etc. on video printers, etc. Recording apparatuses based on various principles can be used, such as those that record on a heat-sensitive recording material using heat rays. However, the recording device is not limited to one that visualizes the autoradiograph obtained as described above, but also records one-dimensional or two-dimensional positional information of the radiolabeled substance in the sample as described above. It is also possible to record it in a desired form, for example by converting it into numbers or symbols. Regarding the method for reading out the radiolabeled substance in the sample accumulated and recorded on the stimulable phosphor sheet in the present invention, the readout operation consisting of the pre-reading operation and the main reading operation was explained above, but the method used in the present invention is as follows. The read operations that can be performed are not limited to the above examples. For example, if the content of the radioactive substance in the sample, its radiation intensity, and the exposure time of the stimulable phosphor sheet for the sample are known in advance, the prereading operation can be omitted in the above example. Furthermore, as a method for reading out the positional information of the radiolabeled substance in the sample stored and recorded on the stimulable phosphor sheet in the present invention, it is of course possible to use an appropriate method other than those exemplified above. . In this way, the positional information stored and recorded in the two phosphor layers is read out from both surfaces of the stimulable phosphor sheet, and then subtraction processing is performed to differentiate the radioactive labels. Location information about each substance can be obtained. In the above description, the case of reading out from both sides of the stimulable phosphor sheet has been described, but the method of reading out the sheet of the present invention is not limited to the above method. It is also possible to read out from one side at the same time by changing the body so that the wavelength region of the main stimulated luminescence does not overlap in each phosphor layer. In this case, it is necessary to separate the stimulated luminescence emitted from the stimulable phosphor sheet in the same position within the photoelectric conversion device and then process it as separate signals. Therefore, even if there are three or more phosphor layers, it is possible to read out each layer and obtain positional information for each radioisotope in a sample containing two or more radiolabeled substances. Is possible. In the autoradiographic recording method using the stimulable phosphor sheet laminate of the present invention, the positional information of the radiolabeled substance stored in the sheet laminate is read out for each sheet as shown in FIG. This can be done as described above using a reading device. Then, the obtained position information can be recorded and saved as an image, or in a desired form such as numerical values or symbols. Therefore, by using the stimulable phosphor sheet or stimulable phosphor sheet laminate of the present invention,
Autoradiographs of samples containing many types of radiolabeled substances that are recognized differently can be recorded as visible images for each radiolabeled substance (radioisotope), and positional information of the radiolabeled substances in the sample can be recorded. This makes it possible to obtain each radiolabeled substance in a desired form. Furthermore, by using the autoradiographic recording method of the present invention using a stimulable phosphor sheet (or a stimulable phosphor sheet laminate), it is possible to record an autoradiograph of a sample multiplexed with radioactive elements in units of radioactive elements. It can be imaged with Furthermore, by subjecting the obtained position information of the radiolabeled substance to electrical signal processing and/or digital signal processing (computer processing), it becomes possible to directly obtain it in the form of desired numerical values, symbols, etc.

[Brief explanation of the drawing]

1A to 1D are schematic cross-sectional views showing embodiments of the stimulable phosphor sheet of the present invention. 1a, 4a, 1b, 1c, 4c, 1d: protective film, 2a, 2b, 2c, 2d: first phosphor layer, 3
a, 3d, 3c, 3d: second phosphor layer, 5b, 5
d: Support, 6c, 6d: Intermediate layer. 2 are schematic cross-sectional views showing embodiments of the stimulable phosphor sheet laminate of the present invention. a, b: stimulable phosphor sheet, c: barrier, 1
a, 1b: protective film, 2a, 2b: phosphor layer, 3
a, 3b: Support. FIG. 3 shows an example of a reading device (or reading device) for reading the positional information of the radiolabeled substance in the sample stored and recorded on the stimulable phosphor sheet in the present invention. 1: stimulable phosphor sheet, 2: readout section for pre-reading, 3: readout section for main reading, 4: laser light source,
5: laser beam, 6: filter, 7: optical deflector, 8: plane reflecting mirror, 9: transport direction, 10: pre-reading light guide, 11: photodetector, 12: amplifier,
13: control circuit, 14: laser light source, 15: laser light, 16: filter, 17: beam expander, 18: optical deflector, 19: plane reflector, 20: fθ lens, 21: transport direction, 22: Main reading light guide, 23: photodetector, 24: amplifier, 25: A/D converter, 26: signal processing circuit.

Claims (1)

[Scope of Claims] 1. Tissues of living organisms and tissues and/or tissues of living organisms.
or an autoradiographic recording method comprising obtaining positional information of a plurality of radiolabeled substances contained in a sample selected from the group consisting of media containing substances derived from biological bodies, By overlapping a stimulable phosphor sheet having a plurality of phosphor layers containing an exhaustible phosphor for a certain period of time, a sample can be The phosphor layer closer to the sample preferentially absorbs radiation from the radioactive label that emits radiation with lower average energy, and the phosphor layer farther from the sample emits radiation with higher average energy. a step of preferentially absorbing radiation from a radiolabeled substance; (2) exciting the plurality of phosphor layers of the stimulable phosphor sheet with electromagnetic waves to release the radiation energy stored and recorded in each phosphor layer; (3) obtaining image signals corresponding to each phosphor layer by emitting photostimulated light and detecting each of the photostimulated lights; and (3) by performing subtraction processing between each image signal. . Obtaining positional information for each of a plurality of types of radiolabeled substances in the sample; An autoradiographic recording method characterized by comprising: 2. The stimulable phosphor sheet has two phosphor layers, and the thickness of one of the phosphor layers is equivalent to the maximum range of radiation from a radiolabeled substance that emits radiation with low average energy. or slightly larger than that, and in the step (1) above, the sample and the stimulable phosphor sheet are superimposed with the phosphor layer placed on the sample side. The autoradiograph recording method according to scope 1. 3. The above-mentioned stimulable phosphor sheet has two phosphor layers and an intermediate layer provided between them, and the total thickness of one phosphor layer and the intermediate layer is such that it emits radiation with low average energy. The maximum range of radiation emitted from the radiolabeled substance is equal to or slightly larger than the maximum range of radiation, and in the step (1) above, the sample and the stimulable phosphor sheet are superimposed on the phosphor layer. 2. The autoradiographic recording method according to claim 1, wherein the autoradiographic recording method is carried out by being placed on the side. 4. The radiolabeled substance that emits radiation with low average energy is radiolabeled with at least one radioisotope selected from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S. An autoradiographic recording method according to any one of claims 1 to 3, characterized in that: 5. Any one of claims 1 to 3, characterized in that in the step (2) above, excitation by electromagnetic waves and detection of photostimulated light are performed on both sides of the stimulable phosphor sheet. Autoradiograph recording method described in section. 6. The autoradiograph according to any one of claims 1 to 3, characterized in that in the step (3) above, position information for each of a plurality of radiolabeled substances is obtained as an image. Recording method. 7 In the step (3) above, the position information for each of multiple types of radiolabeled substances is
The autoradiograph recording method according to any one of claims 1 to 3, characterized in that the autoradiograph is obtained as a numerical value or as a numerical value. 8 Tissues of living organisms and tissues of living organisms and/or
or an autoradiographic recording method comprising obtaining positional information of a plurality of radiolabeled substances contained in a sample selected from the group consisting of media containing substances derived from biological bodies, By overlapping a laminate having a plurality of stimulable phosphor sheets each consisting of a phosphor layer containing an exhaustible phosphor for a certain period of time, the energy level of the radiation emitted from each of the above-mentioned multiple types of radiolabeled substances can be adjusted. Therefore, the stimulable phosphor sheet closer to the sample is made to preferentially absorb radiation from the radiolabeled substance that emits radiation with lower average energy, and the stimulable phosphor sheet farther from the sample is A step of preferentially absorbing radiation from a radiolabeled substance that emits radiation with higher average energy; (2) Exciting each of the plurality of stimulable phosphor sheets with electromagnetic waves so that the radiation is stored and recorded on the sheet. By emitting radiation energy as photostimulated light and detecting this stimulated light,
Obtaining image signals corresponding to each stimulable phosphor sheet; and (3) performing subtraction processing between each image signal to obtain positional information for each of the multiple types of radiolabeled substances in the sample. An autoradiographic recording method characterized by comprising the step of obtaining; 9 The above stimulable phosphor sheet laminate is composed of two stimulable phosphor sheets, and the thickness of one sheet is such that the maximum range of radiation from a radiolabeled substance that emits radiation with low average energy , and in the step (1) above, the sample and the laminate are overlapped by placing the sheet on the sample side. Autoradiograph recording method described in section. 10 The above-mentioned stimulable phosphor sheet laminate is composed of two stimulable phosphor sheets and a barrier interposed between them, and the total thickness of the one sheet and the barrier is such that it emits radiation with low average energy. The maximum range of radiation from the emitted radiolabeled substance is equal to or slightly larger than that, and in the step (1) above, the sample and the laminate are overlapped by placing the sheet on the sample side. 9. The autoradiographic recording method according to claim 8, wherein the autoradiographic recording method is carried out. 11 The radiolabeled substance that emits radiation with low average energy is radiolabeled with at least one radioisotope selected from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S. Claims 8 to 1 are characterized in that:
The autoradiograph recording method described in any one of item 0. 12. The autoradiograph according to any one of claims 8 to 10, characterized in that in step (3) above, position information for each of a plurality of radiolabeled substances is obtained as an image. Recording method. 13. According to any one of claims 8 to 10, in the step (3) above, position information for each of a plurality of radiolabeled substances is obtained as symbols and/or numerical values. autoradiograph recording method. 14 In a stimulable phosphor sheet having a plurality of phosphor layers made of a binder containing and supporting a stimulable phosphor in a dispersed state, the thickness of the phosphor layer on at least one sheet surface side is ³ H, ¹²⁵ A stimulable phosphor sheet characterized by having a maximum range equivalent to or slightly larger than the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of I, ¹⁴ C and ³⁵ S. 15 Claim 1, wherein the stimulable phosphor sheet has two phosphor layers.
The stimulable phosphor sheet according to item 4. 16 The above stimulable phosphor sheet is sequentially coated with a protective film,
It consists of two phosphor layers and a support, and the thickness of the phosphor layer on the protective film side is ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S.
16. The stimulable phosphor sheet according to claim 15, wherein the stimulable phosphor sheet has a maximum range that is equal to or slightly larger than the maximum range of radiation emitted from one type of radioisotope selected from the group consisting of. 17 The layer thickness of the phosphor layer on the surface side of the sheet is 10
The stimulable phosphor sheet according to any one of claims 14 to 16, wherein the stimulable phosphor sheet has a thickness in the range of 250 μm. 18. A stimulable phosphor sheet comprising a plurality of phosphor layers made of a binder containing and supporting stimulable phosphor in a dispersed state, and an intermediate layer provided at at least one location between these phosphor layers, at least The total layer thickness from the surface of one sheet to the intermediate layer is equivalent to the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S, or A stimulable phosphor sheet that is slightly larger than that. 19. The stimulable phosphor sheet according to claim 18, wherein the stimulable phosphor sheet has two phosphor layers and an intermediate layer provided between them. 20 The above stimulable phosphor sheet is sequentially coated with a protective film,
Consists of a first phosphor layer, an intermediate layer, a second phosphor layer, and a support, and the total layer thickness from the surface of the protective film to the intermediate layer is from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C, and ³⁵ S. 20. The stimulable phosphor sheet according to claim 19, wherein the stimulable phosphor sheet has a maximum range that is equal to or slightly larger than the maximum range of radiation emitted from a selected type of radioactive isotope. 21. Accumulability according to any one of claims 18 to 20, characterized in that the total layer thickness from the surface of one of the sheets to the intermediate layer is in the range of 10 to 250 μm. phosphor sheet. 22 In a laminate having a plurality of stimulable phosphor sheets containing a stimulable phosphor, at least one sheet has a thickness selected from the group consisting of ³ H, ¹²⁵ I, ¹⁴ C and ³⁵ S. A stimulable phosphor sheet laminate having a maximum range equal to or slightly greater than the maximum range of radiation emitted from a radioactive isotope, and characterized in that the sheet is placed on the surface side of the laminate. 23. Claim 2, wherein the stimulable phosphor sheet on the surface side of the laminate is composed of a protective film, a phosphor layer, and a support in this order.
The stimulable phosphor sheet laminate according to item 2. 24. The stimulable phosphor sheet laminate according to claim 22 or 23, wherein the stimulable phosphor sheet on the surface side of the laminate has a thickness in the range of 10 to 250 μm. 25 In a laminate having a plurality of stimulable phosphor sheets containing a stimulable phosphor, a barrier is interposed at least at one place between these sheets, and the surface of one laminate including the barrier is The total thickness up to the barrier is ³ H, ¹²⁵ I, ¹⁴ C and
A stimulable phosphor sheet laminate, characterized in that the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of ³⁵ S is equal to or slightly larger than the maximum range. 26. The stimulable phosphor sheet laminate according to claim 25, wherein the barrier is made of a plastic sheet. 27. The stimulable phosphor according to claim 25 or 26, wherein the total thickness from the surface of the one laminate to the barrier including the barrier is in the range of 10 to 250 μm. sheet laminate.