JPS6277336A - Reagent for diagnosing cancer - Google Patents

Abstract

PURPOSE:A reagent for diagnosing cancer capable of emitting fluorescence in a specific wavelength range and visually catching a cancerous site, having good selectivity for cancerous cells, containing sodium fluorescein and ATP as main components. CONSTITUTION:Sodium fluorescein[C20H10NA1O5] has high fluorescence yield on light irradiation in a fixed wavelength range and high selectivity for cancerous cells. This time a reagent for diagnosing cancers, which selectively introduces sodium fluorescein into the cancerous cell, can form a bright, readily observable fluorescent image and makes cancer occurrence site of organism precisely visible by coaction of an enzyme specific to a cencerous cell membrane, is obtained by blending sodium fluorescein with ATP.

Description

[Detailed Description of the Invention] [Field of Application] The present invention has good selectivity for cancer cells and emits fluorescence when irradiated with light in a specific wavelength range.

The present invention relates to a cancer diagnostic reagent that can visually detect cancer sites in living tissues.

[Prior art]

There is a method using fluorescent reagents as a method for diagnosing cancer sites in vivo. This method involves administering a fluorescent reagent with selectivity to cancer cells in vivo, and waiting until a significant difference occurs between the concentration of the fluorescent reagent in normal cells and that in cancer cells. The aim is to visually capture the site that emits fluorescence, that is, the cancer site, by irradiating the reagent with light at a wavelength within the fluorescence excitation range of the reagent.

Hematoporphyrin derivatives are conventionally known as such fluorescent reagents. Once this reagent is administered, it is distributed throughout the body's tissues, but the metabolism of this substance is slower depending on the area, and this difference in metabolic rate is used to diagnose cancer sites. It is.

In other words, it is remarkable that the metabolic action of the substance in cancer cells is generally slower than that in normal cells, and although it has flowed out from normal cells, the fluorescence of the substance remains in cancer cells. The aim is to diagnose cancer sites by irradiating light in the excitation wavelength range.

[Problem that the invention seeks to solve]

However, the above conventional drugs have the following problems.

That is, B. There is a problem with selectivity to cancer cells6. For example, the cancer diagnosis using hemadoporphyrin derivatives mentioned above attempts to utilize the retention of the substance in cancer cells due to the slow rate of metabolism in the cells. In other words, it attempts to utilize the difference in the outflow rate of the above-mentioned substances from cancerous tissue and normal tissue. In other words, it attempts to excite fluorescence in the substance that remains in cancerous tissue where the lymphatic system does not function effectively even if it has flowed out from normal cells, and the substance essentially has no effect on cancer cells. It does not necessarily have selectivity.

Therefore, in reality, it is difficult to accurately grasp the state in which cancer cells remain, and even in the dying stages, it takes a long time (2 to 3 days) for such a state to occur. Currently, the burden on patients and others during this period is significant.

In addition, since this hematoporphyrin derivative does not essentially have selectivity for the constituent elements of cancer cells, it does not stay in some areas where cancer occurs, that is,
In many cases, cells are shed at the same rate as normal cells. Conversely, in the liver and the like, even if the cells are normal, they stay there for about the same amount of time as cancer cells.

In short, with this substance, it is difficult to excite fluorescence in cancer cells accurately and quickly when necessary.

B. Suppose the above-mentioned hematoporphyrin derivative.

Even if light is irradiated at a time when it stays only in cancer cells, the fluorescence intensity of the substance is extremely weak and requires a high-intensity excitation light source and a highly sensitive detector, so it is difficult to detect the cancer site under the actual field of view. It is difficult to confirm this and it is impossible to perform surgery while observing fluorescence.

C. Furthermore, since the above-mentioned hematoporphyrin derivatives inherently have low fluorescence yields, large doses are required, which poses a problem of side effects such as photosensitivity.

That is, when such a large amount of hematoporphyrin derivative is administered, it remains in the normal subcutaneous tissue for a long time, and when exposed to light, a photochemical reaction occurs, resulting in severe sunburn, hives, etc. all over the body.

[Summary of the invention]

This invention was made to solve the above-mentioned problems, and consists of sodium fluorescein and adenosine diphosphate as main components. The purpose of the present invention is to provide a cancer diagnostic reagent that selectively incorporates into cancer cells, enables a bright and easily visible fluorescent image, and allows accurate visual determination of the site of cancer occurrence in a living body.

[Configuration and action]

The cancer diagnostic reagent according to this application uses sodium olecein (C20HIo
NA205) and adenosine diphosphoric acid [CliJe], which forms a pathway from the outside of the membrane to the inside of the cancer cell membrane when it is denatured by the decomposition action of an enzyme specific to cancer cells, allowing the above sodium fluorescein to be easily taken into the cell.
It is a drug whose main component is N5 (113P3). The mechanism of action is as follows.

B. Sodium fluorescein easily emits fluorescence when exposed to light within a certain wavelength range, and is taken into cancer cells along with water through the combined action of adenosine diphosphate and ATPase on the cancer cell membrane.

B. Adenosine triphosphate (ATP) facilitates the entry of sodium fluorescein into cell membranes when it is broken down to adenosine diphosphate (ADP) by ATPase, which is specific to cancer cell membranes, using sodium ions. .

C. Here, we will summarize the process of uptake of the reagent into cancer cells. When a large amount of ATP is present in the surrounding environment, ATPase, which is present in the cell membrane on the crotches of cancer cells, uses sodium ions (sodium fluorescein) to decompose ATP into ADP (adenosine diline #). The cooperation between ATPase and sodium ions in this decomposition action takes place in such a way that sodium ions are drawn into the cell membrane from outside the cell membrane. Fluorescein, a fluorescent substance, is taken into cells along with water through this route.

On the other hand, since the above-mentioned ATPase does not exist in normal cells, it is not taken into the cells and is quickly excreted by the active sodium metabolism function of normal tissues.

〔Example〕

In this example, (C20HID Na2O5] (sodium fluorescein) and CCIOHI3 N5 D+
= P3] (adenosine triphosphate) constitutes the main reagent component, and when irradiated with excitation light of 300 nm to 500 nm, it was approximately 510 nm, which is extremely easy to observe even for humans.
An extremely clear fluorescent image with a yellow-green peak of m was obtained.

〔Effect of the invention〕

The present invention can obtain the following effects through the above-described structural action.

B. Since it has woody selectivity for cancer cells, it stays only in the cancer site, allowing accurate site diagnosis.

B. Since it is not taken up by normal cells, it is quickly excreted from normal tissue, allowing for rapid diagnosis of cancer sites.

C. Because the fluorescence intensity is high, there is no need for a special light source such as a laser or a highly sensitive measurement device such as an SIT camera.

Two, -! Since the 'h-light image is extremely clear, observation under the real field of view with the naked eye is possible, and surgery, etc., can be performed under the visual recognition of the fluorescent image.

Claims (1)

[Claims] A cancer diagnostic reagent whose main ingredients are sodium fluorescein and adenosine triphosphate.