JPS6293679A - Autoradiograph recording method or storing type fluorescent sheet or storing type fluorescent sheet laminate used therein - Google Patents

Abstract

PURPOSE:To obtain the positional information of the radioactive marker substance in a specimen in a desired form for every radioactive marker substance, by using a storing type fluorescent sheet laminate having a plurality of fluorescent layers containing an stimulable phosphor as a photosensitive material. CONSTITUTION:A storing type fluorescent sheet laminate consists of a first storing type fluorescent sheet (a) and a second storing type fluorescent sheet (b). Further, the first storing type fluorescent sheet (a) consists of a protective layer 1a, a phosphor layer 2a and a support 3a while the second storing type fluorescent sheet (b) consists of a protective layer 1b, a phosphor layer 2b and a support 3b. The thickness of at least one sheet is made almost equal to or slightly larger than the max. range of radioactive rays emitted from one radioactive isotope selected from a group consisting of <3>H, <125>I, <14>C and <35>S.

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 and identify a living body or a sample made of a living body-derived substance by obtaining positional information of the living body or a sample made of a substance derived from a living body that has been radioactively labeled. 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 biological body or a part of the tissue of the biological body is used as a sample, and the sample is overlaid with a radiation film such as a high-sensitivity X-ray film for a certain period of time to sensitize (or expose) the film, Autoradiography (also referred to as radioautography), ie, autoradiographic measurement method, which consists of obtaining positional information of a radiolabeled substance in the sample from the photosensitive site, has been known for a long time. This autoradiography is used, for example, to study in detail the metabolism, absorption, and excretion routes and conditions of administered substances in living organisms. There is.

Biochemistry Experiment Course 6 Tracer Experiment Method (Part 1) 271-2
p. 89, "8. Autoradiography - 1 Sueyoshi Wei 1 Akiyo Shigematsu (1977, published by Tokyo Kagaku Dojin) In recent years, autoradiography has been used to treat polymeric substances derived from living organisms such as proteins and nucleic acids. It is also effective for obtaining positional information of a radiolabeled substance on a support medium obtained by attaching a radiolabel and separating and developing the radiolabeled polymer substance, its derivative, or its fragment by gel electrophoresis etc. 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 a double labeling 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 chemical reactions in living organisms by obtaining

As a radiographic film for autoradiography using such a double labeling method, for example, Japanese Patent Publication No. 47-4
No. 5540 discloses that tritium (3H
) and other radioactive isotopes, a silver halide photographic light-sensitive material for color Φ autoradiography is disclosed.

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 on a single radiographic film as a dye image with a different color, so researchers can Only individual autoradiographic images must 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 using autoradiography in practice.

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 hours to several days). This is because the samples that autoradiographs measure are generally not labeled with high radioactivity.

Second, this exposure operation is typically performed at low temperatures (e.g., 0°C
The point is that it must be carried out at a temperature of ~-80°C). The reason for this is that at relatively high temperatures such as room temperature, the latent image in the silver salt on the film formed by exposure to radiation or fluorescence tends to deteriorate, resulting in an image that cannot be developed.
This is because components harmful to the silver salt are likely to migrate from the sample and cause chemical fog to form.

Thirdly, in order to prevent deterioration of image quality due to chemical fog or the like, a sample containing a radiolabeled substance must be exposed in a dry state while being superimposed on a radiation film. For this reason, the sample is usually dried or packaged with a synthetic resin film or the like.

If such fogging occurs in an image obtained by autoradiography, the accuracy of the positional information of the radiolabeled substance will be significantly reduced. For the above reasons, autoradiography operations are complicated.

In addition, the silver salt of the photosensitive component of radiographic film has the disadvantage that it is susceptible not only to chemical stimulation but also to physical stimulation associated with operations such as moving and installing the film, which also makes autoradiography difficult. and cause a decrease in its 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 radiation film,
It requires a high degree of skill and care in its handling, resulting in further complexity of the autoradiographic operation.

Furthermore, conventional autoradiography involves long exposure operations as described above.

There is a problem in that natural radioactivity contained in samples other than radiolabeled substances and exposure of radioactive films reduce the accuracy of the obtained positional information of radiolabeled substances. In order to eliminate such interference due to 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 the 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. Ta. In particular, as mentioned above, it is not easy to obtain positional information about many types of radiolabeled substances from -1 sheets of radiation film.

[Summary of the Invention] As a result of intensive research aimed at solving the above-mentioned problems associated with conventional autoradiography, especially autoradiography using the double labeling method, the present inventor has discovered that radiation-sensitive materials can be used as photosensitive materials. By using a stimulable phosphor sheet or a stimulable phosphor sheet a-layer body in which multiple phosphor layers containing stimulable phosphor are polished instead of a film, the above problems can be solved or the drawbacks can be reduced. The inventors have discovered that this can be realized, and have arrived at the present invention.

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 consisting of.

(2) By overlapping the sample and a stimulable phosphor sheet having a plurality of phosphor layers containing stimulable phosphor for a certain period of time, radiation emitted from each of the plurality of radiolabeled substances listed in J. Depending on the energy level of the sample, the phosphor layer closer to the sample will preferentially absorb radiation from the radiolabel/marker that emits radiation with lower average energy, and the phosphor layer farther from the sample will absorb radiation preferentially The layer has a length L that preferentially absorbs radiation from a radiolabeled substance that emits radiation with a higher average energy; 2) The plurality of phosphor layers of the stimulable phosphor sheet are excited by electromagnetic waves to generate each phosphor. 3) obtaining image signals corresponding to each phosphor layer by emitting the radiation energy stored and recorded in each layer as photostimulated light and detecting each of the photostimulated lights; and 3) each image signal The present invention provides an autoradiographic recording method characterized by comprising the steps of: (1) obtaining positional information for each of a plurality of radiolabeled substances in the sample by performing subtraction processing between the steps;

The present invention also provides a stimulable phosphor sheet used in the autoradiographic recording method described in E, that is, a stimulable phosphor sheet having a plurality of phosphor layers made of a binder containing and supporting stimulable phosphors in a dispersed state. In the phosphor sheet, the layer thickness of the phosphor layer on the surface side of at least one sheet is 3H, I2s
The present invention also provides 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 radioisotope selected from the group consisting of (2), 1A C, and nS. .

Furthermore, the present invention provides, in the above autoradiographic recording method, a stimulable phosphor sheet having a plurality of phosphor layers containing a stimulable phosphor instead of a stimulable phosphor sheet.

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 a-layer 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.

[9. Bright configuration] The stimulable phosphor sheet of the present invention is also called a radiation image conversion panel, and examples thereof include, for example, Japanese Patent Application Laid-Open No. 1986-
It is described in Japanese Patent No. 12145, etc., and its general configuration is already known.

That is, the stimulable phosphor sheet is made of stimulable phosphor, and the radiation energy transmitted through the subject or emitted from the subject is absorbed by the stimulable phosphor of the sheet, 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 released as fluorescence. . Therefore, a radiation image of a subject or subject is obtained by photoelectrically reading this fluorescence and converting it into an electrical signal, and transmitting the obtained electrical signal to a recording material such as photographic film or a CRT.
It can be reproduced as a visible image on a display device such as, or expressed as numerical or recorded northernmost position information.

According to the method of the present invention, in autoradiography using a multiple labeling method, a stimulable phosphor containing a stimulable phosphor is used instead of a radiation film used in conventional autoradiography. By using a sheet or a stack of stimulable phosphor sheets, positional information on samples 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.

In addition, when a stimulable phosphor sheet is used as a photosensitive material, there is no need to image it in order to obtain positional information of the radiolabeled substance imprinted on the stimulable phosphor sheet; By scanning the phosphor sheet with electromagnetic waves such as a laser, it is possible to read out the positional information of the Ox, and convert the positional information into any form such as an image, symbol, and/or numerical value, or a combination thereof. becomes. Furthermore, by further processing the above-mentioned position information using an electrical stage, etc., position information is obtained in various desired forms, that is, the position information is not necessarily obtained in the form of an image, but data processing is performed on the image information. It is also possible to obtain other information obtained by For example, it is possible to obtain information about the target biological system by analyzing electrical or digital signals that indicate the position of a radiolabeled substance obtained by reading out a stimulable phosphor sheet using a computer. be.

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. Therefore, the exposure operation, which was conventionally carried out over a long period of time under cooling, becomes much more convenient, 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 in the use of radiation films, can be virtually eliminated. The fact that this does not occur has a very advantageous effect on improving the accuracy of the obtained position information and on workability. Also,
Deterioration in accuracy due to radioactivity of impurities contained in the sample or natural radioactivity can be easily reduced or eliminated by electrically processing the position information recorded on the stimulable phosphor sheet. It becomes possible to eliminate the problem.

Next, the stimulable phosphor sheet and ta-type phosphor sheet [one-layer body] of the present invention, which can be suitably used in the 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.
A transparent protective film is generally provided on the surface (not facing the support) to protect the phosphor layer from chemical deterioration or physical If.

Typical embodiments of the stimulable phosphor sheet of the present invention include:
An embodiment as shown in FIG. 1 can be mentioned. Note that FIG. 1 is a sectional view showing an embodiment of a stimulable phosphor sheet.

1) A stimulable phosphor sheet consisting of a protective film 1a, a first phosphor layer 2a, a second phosphor layer 3a and a protective film 4a [FIG. 1(a)].

2) A stimulable phosphor sheet [FIG. 1(b)] consisting of a protective film 1b, a first phosphor layer 2b, a second phosphor layer 3b, and a support 5b in this order.

3) Protective film 1c, first phosphor layer 2c, intermediate layer 6C1 in order
A stimulable phosphor sheet consisting of a second phosphor layer 3C and a protective film 4C [Fig. and a stimulable phosphor sheet consisting of a support 5d [Fig. 1(d)]
.

However, the embodiment shown in FIG. 1 is an illustration of a typical embodiment, and the stimulable phosphor sheet of the present invention is not limited to the 78 embodiments of the four types listed in E.

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 stimulable phosphor sheet having the structure shown in 2) [FIG. 1(b)], which is an example of the stimulable phosphor sheet of the present invention, can be manufactured, for example, by the method described below.

The phosphor layer is basically a layer made of a binder containing and supporting particulate stimulable phosphor in a dispersed state.

As mentioned above, a stimulable phosphor is a phosphor that exhibits stimulated luminescence when irradiated with radiation and then irradiated with excitation light.
From a practical point of view, it is desirable that the phosphor be a phosphor that exhibits stimulated luminescence in the wavelength range of 300 to 500 nm by excitation light with a wavelength of 400 to 900 nm (7). The stimulable phosphor used in the body sheet is preferably a divalent europium activated alkaline earth metal fluorohalide phosphor, but is not limited thereto.

Examples of stimulable phosphors used in the stimulable phosphor sheet used in the present invention include:

SrS:Ce, Sm, 5rS4Eu as described in US Pat. No. 3,859,527.

Sm, Th02:E r, and La2O2S:E
u, Sm, Zn described in JP-A-55-12142
S: Cu, P b , B a O11X
A l 20 z :Eu (however, 0.8≦X≦10
), and M 0*xSi02 :A (however, M
l is Mg, Ca, Sr, Zn, Cd, or Ba; A is Ce, Tb, Eu, Tm, Pb, Tl, Bi,
or Mn, and X is 0.5≦X≦2.5)
, described in Japanese Patent Application Publication No. 55-12143 (B a + -x -y,
M g x , Ca y )
F X :aEu” (X is C1 and B
at least one of r, and X and y are 0<
x+y≦0.6. and xy; 1'O, and a is 10
-"≦a≦5X10-2), LnO described in JP-A-55-12144
X: xA (Ln is La, Y, Gd, and Lu
X is at least one of C1 and Br, A is at least one of Ce and Tb, and X is 0<x<0.1).

It is described in Japanese Patent Application Laid-Open No. 55-12145 (B
al-X, M''x) FX: yA
(However, M'' is at least one of Mg, Ca, Sr, Zn, and Cd (7), X is at least one of C1, Br, and I, and A is Eu, Tb, Ce.
, Tm, Dy, Pr, Ha, Nd, Yb, and Er, and X is oxX≦0.6,
y is 0≦y≦0.2).

M” described in Japanese Patent Application Laid-Open No. 55-160078
FX* xA: yLn [However, Mll is Ba
, Ca, Sr, Mg, Zn, and at least one of Cd, A is Bed, MgO, CaO1SrO, B
ad, ZnO, AJJ, O,, Y2O2, La20: +
, In2O3, S 02, TlO□, ZrO2, Ge
O2,5n02,Nb.

06, Ta2O, and The2, and Ln is Eu, Tb, Ce, or Tm.

Dy, Pr, Ho, Nd, Yb, Er, Sm
, and at least one of Gd, X is cL; L,
At least one of Br and I.

X and y are 5X10-'≦X≦0.5° and Okuy≦0.2, respectively] A phosphor represented by the composition formula: CB described in JP-A-56-116777
at-x IM"X)F2 ・aBaX2 :yEu
, zA [where Ml is beryllium, magnesium, calcium, strontium, zinc.

and at least one of cadmium, X is chlorine,
At least one of bromine and iodine, A is at least one of zirconium and scandium, and a, x, y, and Z are each 0.5≦a≦1.
25. A phosphor represented by the composition formula: 0≦X≦1, to-”≦y≦2×10−1, and 0<z≦1O−2.

It is described in Japanese Patent Application Laid-open No. 57-23673 (Ba
, -x, M"X) F1a aBaX2:yEu,z
B [where Ml is at least one of beryllium, magnesium, calcium, strontium, zinc, and cadmium, X is at least one of chlorine, bromine, and iodine, and a, x, y, and 2 are 0.5≦a≦1.25.0≦X≦1.10-'≦, respectively
y≦2xio-' and O<z≦2XIO-'], a phosphor described in Japanese Patent Application Laid-Open No. 57-23675 (Ba
t-x, M'H)F2*aBaX2:yEu
, zA [where MM is at least one of helium, magnesium, calcium, strontium, ffi, and cadmium, X is at least one of chlorine, bromine, and iodine, and A is at least one of arsenic and silicon. -・Species, a, x, y, and Z are each 0.5≦a≦1.25.0≦X≦1.10-6≦
y≦2×10-' and O<Z≦5xto-'] A phosphor represented by the composition formula: y≦2×10-' and O<Z≦5xto-'
X: xCe [However, M is Pr.

Nd, Pm, Sm, Eu, Tb, Dy, Ho, Er, T
is at least one positive valent metal selected from the group consisting of m, Yb, and Bi, X is either one or both of O and Br, and X is O<x<0
．． A phosphor represented by the composition formula of
, -X M 3172 L X /2 F X : y
E u ” [However, 1M is Li, Na, Rb,
and Cs; L represents Sc, Y, La, Ce, P
r, Nd, Pm, Sm, Gd, Tb, Dy, Ho, Er
, Tm, Yb, Lu, An, Ga, In, and at least one valent metal selected from the group consisting of 1; X represents at least one halogen selected from the group consisting of C1, Br, and I and X is 10-2≦X≦0.5, y is 0 and y≦0.1], and is described in JP-A-59-27980. B a
FX* xA: yE u"" [However, X is CM
, Br, and at least one halogen selected from the group consisting of
, y is o<y≦0.1].

BaF described in JP-A No. 59-47289
X fist x A: yEu” [However, X is C1, Br
, and I; A is from the hexafluoro compound group consisting of monovalent or monovalent salts of hexafluorosilicic acid, hexafluorotitanic acid, and hexafluorozirconic acid; It is a baked product of at least one selected compound; and X is 10-6≦X≦0.1, and y is o<y≦
0.1], a phosphor represented by the composition formula, JP-A-5
BaFXs x described in Publication No. 9-56479
NaX': aEu2° [where X and X' are each at least one of C1, Br, and I, and x'8 and a are 0<X≦2 and 0<a
≦0.2].

Mrin F described in Japanese Patent Application Laid-Open No. 59-56480
X* xNaX':yEu2°:zA [where Ml is at least one alkaline earth metal selected from the group consisting of Ba, Sr, and Ca; X and X'' are Cl and Br, respectively.

and (1) at least one halogen selected from the group consisting of; A is at least one transition metal selected from V, Cr, Mn, Fe, COI and Ni;
and X is O<x≦2, y is o<y≦0.2, and Z is 0<z≦10−2], JP-A-59-75200 M” written in
F X ++ a M ' X ' * b M ”
X"2・c M"
+ is at least one alkali metal selected from the group consisting of Li, Na, Rh, and Cs; MI
is at least one divalent metal selected from the group consisting of Be and Mg; MI is at least one trivalent metal selected from the group consisting of An, Ga, In, and Tl; A is a fully bent oxide and X is at least one kind of halogen selected from the group consisting of Cl, Br, and Br;
, and at least one kind of halogen selected from the group consisting of I; and a is O≦a≦2, and b is 0≦b≦
1O-2, C is O≦C≦1O-2, and a + b +
c≧10−6; X is O<x≦0.5, y is o<
y≦0.2], M”X described in JP-A No. 60-84381
2* aM"X' 2: xEu" [However, Ml
is at least one kind of alkaline earth metal selected from the group consisting of Ba, Sr and Ca; X and X'' are at least one kind of halogen selected from the group consisting of Cl, Br and I;

and X; I'X'; and a is 0.1≦a≦1
0.0, X is 0<x≦0.2. ':xE u "" [
However, MI is at least one alkaline earth metal selected from the group consisting of Ba, Sr, and Ca;
vl I is at least one kind of alkali metal selected from the group consisting of Rh and Cs; X is at least one kind of halogen selected from the group consisting of C1, Br and I; x゛ is F, C9, Br and and a and X are O≦a≦4.0 and 0 (X≦0), respectively;
．． A phosphor represented by the composition formula M'X:xBi [where Ml is selected from the group consisting of Rh and Cs] is is at least one kind of alkali metal; X is at least one kind of halogen selected from the group consisting of C1, Br, and H; Examples include phosphors expressed in

Furthermore, the M '' X 2 dispute a M ''
The X E u ” phosphor may contain the following additives in the following proportions per mole of MNX2·aM”X′2.

bM'X" (where Ml is Rb and C
at least one alkali metal selected from the group consisting of s, X'' is at least one halogen selected from the group consisting of F, C1, Br, and
is o<b≦10.0); Patent application 1987-77225
6 bKX″*-cMgX”
2 meeting dM■X” (However, Ml is Sc, Y, La.

at least one kind of trivalent metal selected from the group consisting of Gd and Lu; X'', x'' and X'' are all at least one kind of halogen selected from the group consisting of F, C1, Br and ■; and c and d are respectively 0≦b≦2゜0.0≦C≦2.0.0≦d≦2
．． 0 and 2 X l O''≦b+C+d);
0-'); bA described in Japanese Patent Application No. 59-84358 (however, A is 5i02 and P2O
at least one kind of oxide selected from the group consisting of 5, where b is to-'≦b≦2 bsfO (wherein b satisfies o<b≦3X10-2);bSnX"2 described in Japanese Patent Application No. 59-240454 (however, X' is a group consisting of F, C1, Br and I); bCsX″ecsnX″2 described in Japanese Patent Application No. 60-78033 filed by the present applicant (however, x ” and xl are each at least one kind of halogen selected from the group consisting of F, C1, Br and engineering, and b and C are o<b≦10.0 and 10-6≦, respectively.
C≦2
CsX''*7Ln'◆ (However, X'' is F, C!; L,
At least one halogen selected from the group consisting of Br and Ln, and Ln is Sc, Y, Ce, Pr, Nd,
Sm.

Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu
at least one rare element selected from the group consisting of, and b and y each satisfy o<b≦10.0.
and 10≦y≦1.8x i o-').

etc. can be mentioned. However, the stimulable phosphor used in the present invention is not limited to the phosphor described in L, but any phosphor that exhibits stimulated luminescence when irradiated with radiation and then irradiated with excitation light. It may be something.

. Examples of binders for the phosphor layer include proteins such as gelatin, polysaccharides such as dextran, or natural polymeric substances such as gum arabic; = IJden/vinyl chloride copolymer, polyalkyl (meth)acrylate, vinyl chloride/
Binders typified by synthetic polymeric materials such as vinyl acetate copolymers, polyurethanes, cellulose acetate butyrate, polyvinyl alcohol, linear polyesters, etc. may be mentioned. 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. be.

Note that these binders may be crosslinked with a crosslinking agent.

The phosphor layer can be formed on the support by, for example, a primary 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, ethyl cellulose, and vinylidene chloride.・Vinyl chloride copolymer,
Examples of binders include synthetic polymeric substances such as polyalkyl (meth)acrylate, vinyl chloride/vinyl acetate copolymer, polyurethane, cellulose acetate butyrate, polyvinyl alcohol, and linear polyester. 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; acetone, methyl ethyl ketone, and methyl isobutyl ketone. Ketones: 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 as follows: 1 to 1: Zo.

(weight ratio), and especially l:8 to 1
:40 (weight ratio).

Coating liquid 71 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. Examples of dispersants used for such purposes may include various additives such as plasticizers for
Examples include phthalic acid, stearic acid, caproic acid, and lipophilic surfactants. Examples of plasticizers include phosphate esters such as triphenyl phosphate, tricresyl phosphate, and diphenyl phosphate; phthalate esters such as diethyl phthalate and dimethoxyethyl phthalate; ethyl phthalyl ethyl glycolate, butyl phthalyl glycolate, etc. and polyesters of polyethylene glycol and aliphatic dibasic acids, such as polyesters of triethylene glycol and adipic acid and polyesters of diethylene 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 of the coating solution.

This coating operation can be carried out using a conventional coating f-stage, for example, a doctor blade, roll coater, knife coater, etc.

As a support, an intensifying screen (
The material can be arbitrarily selected from various materials used as supports for stimulable phosphor sheets (or intensifying screens) or materials known as supports for stimulable phosphor sheets. Examples of such materials are:

Films of plastic materials such as cellulose acetate, polyester, polyethylene terephthalate, polyamide, polyimide, triacetate, polycarbonate, metal sheets such as aluminum foil, aluminum alloy foil, ordinary paper, baryta paper, resin coated paper, pigments such as titanium dioxide, etc. Examples include pigment paper containing polyvinyl alcohol and sizing paper containing polyvinyl alcohol. 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 a 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, the side on which the phosphor layer is provided 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. A polymer material such as gelatin is coated on the surface of the support to form an adhesive external layer, or a light reflective layer made of a light reflective material such as titanium dioxide, or a light absorbing material such as carbon black is used. The support used in the present invention may also be provided with an absorbent layer.These various layers can also be provided on the support used in the present invention.

Furthermore, as disclosed in JP-A-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 adhesive layer, a light-reflecting layer, a light-absorbing layer, or a metal foil is provided, irregularities may be formed on the surface (meaning the surface thereof).

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. It is preferable to provide it directly to the

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 intended stimulable phosphor sheet, the type of phosphor particles, the mixing ratio of the binder and the phosphor particles, etc., but is usually 5 μm to inch. However, the thickness of this layer is preferably 10 to 500 pm.

Note that the second phosphor layer does not necessarily have 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 accumulate radiation from radioactive elements with low average energy in the first phosphor layer placed on the sample side when using a storage phosphor sheet, it is necessary to The stimulable phosphor preferably 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, the first phosphor layer contains a low-energy absorption material such as a metal (Cu, W, Mo, Nf, Pb, etc.). It may be contained.

Next, a protective film is provided on the first phosphor layer. This protective XIK film is formed by, for example, adhering a transparent R film separately formed from polyethylene terephthalate, polyethylene, vinylidene chloride, polyamide, etc. to the surface of the first phosphor layer using a suitable adhesive. can do. Alternatively, the protective film may be made of 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 axed vinyl/vinyl acetate copolymer. It can also be formed by applying a solution prepared by dissolving a molecular substance in an appropriate solvent onto the surface of the first phosphor layer. The thickness of the transparent protective film thus formed is usually about 0.1 to 50 pm, preferably 0.1 to 50 pm.
It is desirable to set it as 3 to 20 meters.

The stimulable phosphor sheet produced in this way has a special feature of
As described in Japanese Patent No. 55-163500 and Japanese Patent Application No. 55-171545 filed by the present applicant, at least a portion of the stimulable phosphor sheet is suitable for increasing the sharpness of the resulting stimulable phosphor sheet. It may be colored with a coloring agent.

When an intermediate layer is provided between the phosphor layers as shown in FIG. This can be done by applying a dissolved solution to the phosphor layer.

Alternatively, in a stimulable phosphor sheet having the structure as shown in FIG. 1(e), 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 a radioactive element with low average energy. In other words, the radiation from the radioactive element with low average energy is absorbed only by the phosphor layer on the sample side with the intermediate layer as a boundary, and is not absorbed by the phosphor layer on the opposite side. It is something. 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. However, the thickness of this layer is preferably 3 to 2001 m, and the material used for the intermediate layer preferably has a high density.

Hereinafter, this intermediate layer may have enhanced absorption characteristics for low-energy radiation by containing a metal such as Cu, W, Mo, Ni, or Pb.

In addition, when the intermediate layer reads out each phosphor layer of the stimulable phosphor sheet from both sides of the sheet as described later, it is possible to simultaneously read out the #exhausted luminescence from the phosphor layers below the intermediate layer. 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 radioactive isotopes 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, 12S1, +4C,
3S3, :12p can be mentioned. 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 transferred to the phosphor layer on the sample side (in the configuration shown in Figure 1 (b)). In order for the radiation from the other radioactive element to be mainly absorbed by the phosphor layer on the side far from the sample (also the second phosphor layer), the first phosphor layer The layer thickness is set to 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 layers of the first phosphor layer differ depending on the combination of radioactive elements. The thickness is preferably equal to or slightly greater than the maximum range of radiation from radioactive elements that emit low-energy radiation. Radiation m emitted from the above radioactive isotopes
The maximum range of (beta rays, however, X-rays in 3 cases) 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, it is particularly preferable that the thickness of the phosphor layer on the sample side be within the range shown in Table 1.

Table 1 Average energy Maximum range of phosphor layer (MeV)
(g/rn') Layer thickness (J-11) HO,
0055910~15'' IO,00410~15 1AG O,049176200~250''S
(1,048195200~25032P
O, fi95 4822 The phosphor layer may have one layer having the above layer thickness, or the sum of multiple layers may have the above layer thickness, or a protective film, middle 81 layer, etc. are provided, the total layer thickness including those layers should be the above-mentioned layer thickness. For example, if the radioactive diffraction elements contained in the sample are 2H and 4C, and the stimulable phosphor sheet has the configuration shown in FIG. 1(b), the thickness of the protective film is set to 0°. 3 to I μm, the layer thickness of the first phosphor layer is 10-15 m, and the layer thickness of the second phosphor layer is 1 μm.
For example, when the radioactive elements contained in the sample are 1A C and 32 P and the stimulable phosphor sheet has the configuration shown in FIG. 1(d), , the thickness of the protective film is 0.5 to 10 pm.
.

The thickness of the first phosphor layer is 100 to 150 pm, the thickness of the intermediate layer is 50 to 200 μm, and the total thickness of the protective film, first phosphor layer, and intermediate layer is 200 to 300 μm. and the layer thickness of the second phosphor layer is 100 to 300 Bm.
It is preferable that

The type and mixing ratio of the stimulable phosphor contained in each phosphor layer are preferably selected depending on the type and combination of target radioactive elements, their radiation intensity, etc. It is appropriately selected in relation to the layer structure of the stimulable phosphor sheet, such as the thickness of one layer.

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) First stimulable phosphor sheet a (protective film fa.

A sheet laminate consisting of a phosphor layer 2a, a support 3a) and a second stimulable phosphor sheet b (protective film 1b, phosphor layer 2b, support 3b) [Fig. Mono-stimulable phosphor sheet a (protective film 1a, phosphor layer 2a, support 3a)
, barrier C and second stimulable phosphor sheet b (protective film 1
b, phosphor layer 2b, and support 3b) [FIG. 1 (2)] However, the two embodiments shown in FIG. The stimulable phosphor sheet laminate of the present invention is not limited to the following two embodiments. For example, the number of stimulable phosphor sheets constituting the stimulable phosphor sheet laminate of the present invention is limited to two. It may be composed of three or more stimulable phosphor sheets, and if there are three or more stimulable phosphor sheets and a barrier is provided between them, the barrier is the space between each sheet. It is sufficient if it is provided in at least one location.

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 in 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. 2 (1),
The support for the first stimulable phosphor sheet (a) on the sample side can also serve as a barrier, and therefore the support may contain the above-mentioned low energy absorbing substance.

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.

In addition, a plurality of stimulable phosphor sheets may have the above-mentioned thickness, and if a barrier is further provided, the total thickness including the barrier may be the thickness specified in the above. , RT for mainly absorbing radiation from radioactive isotopes that emit radiation with low average energy.
A stimulable phosphor sheet (or a stimulable phosphor sheet and a barrier, hereinafter the same) is placed on the outside, and a stimulable phosphor sheet is used to mainly absorb radiation from radioactive isotopes that emit radiation with higher average energy. By sequentially planting layers, the stimulable phosphor sheet laminate of the present invention is prepared.

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 configuration as described above.
Preferred (can be implemented).

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. The method is carried out by overlapping the 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, examples of the medium containing biological tissues and/or biologically derived substances include support media in which biopolymer substances such as proteins, nucleic acids, derivatives thereof, and decomposition products thereof are separated and developed. be able to.

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 radioisotope used in the present invention includes radiation (α rays, β rays,
Any type of nuclide may be used as long as it emits γ-rays, neutron beams, X-rays, etc.; representative examples include the aforementioned H and L? s1.14c, 3SS, “p)”
The sample to be recorded in the present invention is
It has multiple types of radiolabeled substances radiolabeled with at least two different types of radioactive elements.

In the exposure operation, the above-mentioned sample is superimposed on a stimulable phosphor sheet either as it is or after undergoing any treatment such as dry bombing 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. 1(a) to 1(d), 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 laminates shown in FIGS. 2(1) and 2(2), the stimulable phosphor sheet (a) is placed on the sample side. When using a sheet laminate having a barrier C as shown in FIG. By exposing the stimulable phosphor sheet b and the sample with the barrier C in between and exposing them to light, radiation from radioactive isotopes with different energy intensities is sequentially applied to the stimulable phosphor sheet b and the sample. It is also possible to absorb and accumulate on a sheet.

In addition, the so-called exposure time depends on the type of radioisotope contained in the sample, its radiation intensity; the concentration of the radiolabeled substance;
Density: Although it varies depending on the sensitivity of the stimulable phosphor sheet, the positional relationship between the sample and the stimulable phosphor sheet, etc., the exposure operation requires the tool 1 for a certain period of time, for example, several seconds. However, when the Mu-based 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 information as much as possible by performing 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.

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 an 8m phosphor sheet consisting of multiple phosphor layers of the present invention is used as a photosensitive material, radiation from a radioactive element with a 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. It can be almost completely absorbed by the side phosphor layer,
In other words, at least radioactive elements with low average energy can be separated by multiple phosphor layers. Therefore, radiation from another radioactive element with high average energy is not efficiently separated and is separated into multiple phosphor layers. Even if the radioactive element is absorbed across the area, the position of each radioactive element can be determined by reading out each phosphor layer as described below, and then performing suitable signal processing such as subtraction on the digital signal obtained from each phosphor layer. You can get information.

In addition, when a stimulable phosphor sheet of the present invention is used as a photosensitive material, a different ?M carcass is used for each radiolabeled substance. Is the radiation energy absorbed by the S-based phosphor sheet? Make it so that it is multiplied by S.

Below, an example of the reading device (or reading device) shown in FIG. 3 will be described regarding the method for reading out the location information of the radiolabeled substance shown in the autoradiograph accumulated and recorded on the stimulable phosphor sheet in the present invention. This will be briefly explained with reference to.

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 (see FIG. 1(a)
~(d), the positional information accumulated and recorded in the first phosphor layer is read out from the surface of the protected @1a~ld).

Figure 3 is for pre-reading to temporarily read 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). The apparatus includes a reading section 2 and a main reading section 3 having a function of reading out the autoradiograph stored and recorded on the sheet 1 in order to output the position information of the radiolabeled substance.

In the prefetch successive section 2, the following prefetch operation is performed.

The laser light 5 generated from the laser light source 4 passes through the filter 6, and in response to excitation by the laser light 5, a portion of the wavelength region corresponding to the wavelength region of stimulated luminescence generated from the stimulable phosphor sheet 1 is removed. is cut. Next is the laser light.

The light is deflected by a light deflection base 7 such as a galvanometer mirror, reflected by a movable surface reflection ta8, and then one-dimensionally deflected and incident on the sea surface L. 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 placed in the direction of the arrow 9 with the protective film (la to ld) side facing up under irradiation with the polarized laser beam 5.
It is transported in the direction of . Therefore, the entire surface of the sheet 1 is irradiated with the polarized laser beam. In addition, the output of the laser light source 4.

The beam diameter of the laser beam 5, the scanning speed of the laser beam 5, and the transport speed of the sheet 1 are 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 l 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. The light enters the pre-reading light guide 10 . The light guide 10 has a linear entrance surface and is placed close to and opposite to the scanning line on the stimulable phosphor sheet 1, and its exit surface forms an annular ring, such as a photomultiply. It is connected to the light receiving surface of light detection=11. This light guide 10 is
For example, it is made by processing a transparent thermoplastic resin sheet such as acrylic synthetic resin, and is configured so that the light incident on the incident surface is totally reflected inside and transmitted to the exit surface. Stimulated luminescence from the stimulable phosphor sheet 1 is guided through the light guide 1O, reaches the exit surface, is emitted from the exit surface, and is received by the photodetector 11.

The preferred shape, material, etc. of the light guide are disclosed in Japanese Patent Application Laid-open No. 1983-
Disclosures are made in JP-A No. 87970, No. 56-11397, and the like.

A filter is attached to the light-receiving surface of the photodetector 11, which transmits only light in the wavelength region of stimulated luminescence and cuts light in the wavelength region of excitation light (laser light), and detects only stimulated luminescence. It is made to be wet. 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 controls the amplification factor setting value a, the recording scale factor b, and the reproduction rate so that an image with the most uniform density and contrast and excellent observation and interpretation performance can be obtained according to the obtained accumulated recording information. Image processing condition setting value C is 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.

Laser light 1 emitted from the main reading laser light source 14
After passing through a filter 16 having the same function as the filter 6 described above, the beam diameter of the beam 5 is precisely adjusted by a beam expander 17. Next, the laser beam is deflected by a light deflector 18 such as a galvanometer mirror, reflected by a plane reflecting mirror 19, and then one-dimensionally deflected and incident on the stimulable phosphor sheet l. Note that an fO lens 20 is arranged between the optical deflector 18 and the plane reflecting mirror 19, so that when the soil of the sheet 1 is scanned by the deflected laser beam, a uniform beam speed is always maintained. .

The stimulable phosphor sheet 1 is maintained under the irradiation of the above-mentioned polarized laser beam in the same manner as in the pre-reading operation.
It is transported in the direction of arrow 21 with the Q side facing up. Therefore,
As in the pre-reading operation, the entire surface of the sheet 1 is irradiated with the polarized laser light.

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. This 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 single 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 range 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 energetic signal, which is amplified into an electrical signal at an appropriate level by the amplifier 24 whose sensitivity is set according to the amplification factor setting value a of the A/D. It is input to the converter 25. The A/D converter 25 converts the digital signal into a digital signal with a scale factor suitable for the signal fluctuation range according to the recording scale factor setting value, and inputs the digital signal to the signal processing circuit 26 .

Further, the same operation as described above is performed 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)). Accordingly, the position information stored and recorded in the second phosphor layer is read out and inputted 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, position information (image signals) obtained by reading a plurality of phosphor layers is stored in a memory (that is, a buffer memory or a nonvolatile memory such as a magnetic disk), and then By performing subtraction processing on the digital signal, that is, by subtracting between corresponding positions of the radiographic image to be subtracted, positional information about the radiolabeled substance can be separated for each radioactive element. The subtraction magnification in subtraction processing is
This determined magnification is multiplied by the zero image signal, which can be determined by calculating from the thickness of the phosphor layer and the radiation energy, or by simultaneously exposing a standard material (reference) and using it as a reference. Later, subtraction is performed between the signals. Regarding the subtraction processing method of radiographic images, for example, the applicant's 4￥￥￥￥￥￥￥￡ffffff-
It is described in detail in the specification of No. 45475. Then,
Based on the reproduced image processing condition setting value C for each of the obtained positional information, the density and contrast are appropriate and the observation interpretation performance is excellent 6 (after signal processing is performed to obtain the master image, The data is transmitted to a recording device (not shown) via storage means.

Examples of recording devices include those that optically record by scanning a photosensitive material with a laser beam, etc., those that electronically display on a CRT, etc., and those that record radiation images displayed on a CRT, etc. on a video printer, etc. Recording apparatuses based on various principles can be used, such as those that record on the heat-sensitive recording material l1 using heat rays.

However, the recording device is not limited to one that visualizes the autoradiograph obtained as described above.
As described above, the one-dimensional or two-dimensional positional information of the radiolabeled substance in the sample can be recorded 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 readout operation that can be performed is not limited to the above example. For example, the readout operation that can be carried out is not limited to the above example. If so, the prefetch 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 applied to each of the radiolabeled substances with different labels. You can get location information about.

In the above, 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 simultaneously emitted from the stimulable phosphor sheet within the photoelectric conversion device and then process it as separate signals. Therefore,
Even if there are three or more phosphor layers, it is not possible to read out each layer, and it is difficult to obtain positional information for each radioisotope for samples containing two or more radioactively labeled substances. It is possible to do so.

In the autoradiographic recording method using the stimulable phosphor sheet laminate of the present invention, the position 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 the stimulable phosphor sheet a carcass of the present invention, an autoradiograph of a sample containing many kinds of radiolabeled substances with different labels can be obtained by using the stimulable phosphor sheet (radioactive isotope). ) can be recorded as a visible image for each radiolabeled substance, and furthermore, it is possible to obtain positional information of the radiolabeled substance in the sample in a desired form for each radiolabeled substance.

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 drawings]

FIGS. 1(a) to 1(d) are schematic cross-sectional views showing embodiments of a stimulable phosphor sheet of the present invention. la, 4a, lb, lc, 4c, ld: protective film 2a, 2
b, 2c, 2d: first phosphor layer, 3a, 3b, 3c, 3
d+ second phosphor layer. 5b, 5d: Support, 6c, 6d: Intermediate layer Fig. 2 (1)
and (2) are schematic cross-sectional views showing embodiments of the stimulable phosphor sheet laminate of the present invention. a, b: M active phosphor sheet, c: barrier, la, lb
: Ho, EffM, 2a, 2b: Phosphor layer. 3a, 3b: Support. FIG. 3 shows an example of a reading device (or reading type 5!1) for reading the positional information of a radiolabeled substance in a sample stored and recorded on a stimulable phosphor sheet in the present invention. l Bi-accumulative phosphor sheet, 2: Readout section for pre-reading, 3: Readout section for main reading, 4: Laser light source, 5: Laser light, 6
: Filter, 7: Light deflector, 8: Plane reflector, 9: Transfer direction, 1o: Pre-reading light guide, 11: Photodetector, 1
2: Amplifier. 13: Control circuit, 14: Laser light source, 15: Laser light, 16: Filter, 17: Beam exchange
118: Optical deflector, 19: Planar reflector, 20: fO lens, 21: Transport direction, 22 Dual reading light guide, 23:
Photodetector, 24: Amplifier, 25: A/D converter, 2
6: Signal processing circuit patent applicant Fuji Photo Film Co., Ltd. Agent Patent attorney Yasuo Yanagawa Figure 1

Claims (1)

[Claims] 1. Position 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, Depending on the energy level of the radiation emitted from each of the radiolabeled substances, the phosphor layer closer to the sample preferentially absorbs the radiation from the radiolabeled substance emitting radiation with lower average energy; a step of causing the phosphor layers on the side farther from the sample to preferentially absorb radiation from a radiolabeled substance that emits radiation with higher average energy; 2) exposing the plurality of phosphor layers of the stimulable phosphor sheet to electromagnetic waves; The step of emitting the radiation energy stored and recorded in each phosphor layer as photostimulated light by exciting the phosphor layer, and detecting each of the photostimulated lights to obtain image signals corresponding to each phosphor layer. and 3) obtaining positional information for each of a plurality of radiolabeled substances in the sample by performing subtraction processing between each image signal. 2. The stimulable phosphor sheet has two phosphor layers,
and the thickness of the single phosphor layer is equal to or slightly larger than the maximum range of radiation from a radiolabeled substance that emits radiation with low average energy, and in the step 1) above, the sample 2. The autoradiographic recording method according to claim 1, wherein the stimulable phosphor sheet and the stimulable phosphor sheet are superimposed with the phosphor layer placed on the sample side. 3. The above-mentioned stimulable phosphor sheet has two phosphor layers and an intermediate layer provided between them, and the total layer thickness of one phosphor layer and the intermediate layer is such that the stimulable phosphor sheet has low average energy radiation. The range is equal to or slightly greater than the maximum range of radiation from a radiolabeled substance that emits
2. The autoradiographic recording method according to claim 1, wherein in step ), the sample and the stimulable phosphor sheet are superimposed with the phosphor layer placed on the sample 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 ^3H, ^1^2^5I, ^1^4C, and ^3^5S. An autoradiograph recording method according to any one of claims 1 to 3, characterized in that the autoradiograph recording method is characterized in that: 5. In the step 2), excitation by electromagnetic waves and detection of photostimulated light are performed on both sides of the stimulable phosphor sheet.
The autoradiograph recording method described in any of the paragraphs. 6. The autoradiograph according to any one of claims 1 to 3, characterized in that in step 3), position information for each of a plurality of radiolabeled substances is obtained as an image. Recording method. 7. The method according to any one of claims 1 to 3, characterized in that in step 3), positional information for each of a plurality of radiolabeled substances is obtained as symbols and/or numerical values. autoradiograph recording method. 8. Automation consisting of obtaining 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 the radiographic recording method, 1) the sample and a laminate having a plurality of stimulable phosphor sheets each consisting of a phosphor layer containing a stimulable phosphor are superimposed for a certain period of time, thereby recording the radioactivity of the plurality of types. Depending on the energy level of the radiation emitted from each labeled substance, 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; a step of causing the stimulable phosphor sheets on the side farther from the sample to preferentially absorb radiation from a radiolabeled substance that emits radiation with higher average energy; 2) exposing each of the plurality of stimulable phosphor sheets to electromagnetic waves; a step of emitting the radiation energy stored and recorded in the sheet as photostimulated light, and detecting the photostimulated light to obtain an image signal corresponding to each stimulable phosphor sheet; and 3) An autoradiographic recording method comprising: obtaining positional information for each of a plurality of radiolabeled substances in the sample by performing subtraction processing between each image signal. 9. The above-mentioned stimulable phosphor sheet laminate is composed of two stimulable phosphor sheets, and the thickness of one sheet is such that the maximum scattering of radiation from a radiolabeled substance that emits radiation with low average energy Claim 8 is characterized in that, in the step 1), the sample and the laminate are superimposed on each other 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 sum of the thicknesses of one sheet and the barrier is such that the stimulable phosphor sheet laminate has a low average energy radiation. The maximum range of radiation from a radiolabeled substance that emits a 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 ^3H, ^1^2^5I, ^1^4C, and ^3^5S. 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), 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), 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 ^3H, ^1^2^5I, ^1^4C and ^3^
A stimulable phosphor sheet 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 5S. 15. The stimulable phosphor sheet according to claim 14, wherein the stimulable phosphor sheet has two phosphor layers. 16. The above stimulable phosphor sheet consists of a protective film, two phosphor layers, and a support in this order, and the thickness of the phosphor layer on the protective film side is ^3H, ^1^2^5I, ^ Claim 1, characterized in that the range is equal to or slightly larger than the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of 1^4C and ^3^5S.
The stimulable phosphor sheet according to item 5. 17. The layer thickness of the phosphor layer on the surface side of the sheet is 10 to 2
The stimulable phosphor sheet according to any one of claims 14 to 16, characterized in that the thickness is in the range of 50 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, The total layer thickness from at least one sheet surface to the intermediate layer is ^3H, ^1^2^5I, ^
A stimulable phosphor sheet 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 1^4C and ^3^5S. 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 stimulable phosphor sheet comprises, in order, a protective film, 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 ^3H
, ^1^2^5I, ^1^4C, and ^3^5S A patent characterized in that the maximum range of radiation emitted from a type of radioisotope selected from the group consisting of A stimulable phosphor sheet according to claim 19. 21. The accumulation 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, the thickness of at least one sheet is ^3H, ^1^2^5I, ^1^4C and ^
The sheet is equal to or slightly larger than the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of 3^5S, and the sheet is placed on the surface side of the laminate. A stimulable phosphor sheet laminate. 23. The stimulable phosphor sheet laminate according to claim 22, wherein the stimulable phosphor sheet on the surface side of the laminate consists of a protective film, a phosphor layer, and a support in this order. body. 24. The stimulable phosphor sheet on the surface side of the laminate has 10
24. The stimulable phosphor sheet laminate according to claim 22 or 23, wherein the stimulable phosphor sheet laminate has a thickness in the range of ~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 barrier is removed from the surface of one of the laminates. The total thickness including the barrier is ^3H, ^1^2^5I, ^1^4C and ^3^5
A stimulable phosphor sheet laminate, characterized in that the stimulable phosphor sheet laminate is equal to or slightly larger than the maximum range of radiation emitted from a type of radioactive isotope selected from the group consisting of S. 26. The stimulable phosphor sheet laminate according to claim 25, wherein the barrier is made of a plastic sheet. 27. Claim 25 or 26, characterized in that 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.
The stimulable phosphor sheet laminate described in Section 1.