KR20210012263A - Synthesis of human EphA2-specific monobody conjugated with a novel radioactive compound for cancer diagnosis and therapy and use thereof - Google Patents

Abstract

The present invention provides a method for manufacturing a human EphA2-specific monobody combined with a novel radioactive compound for cancer treatment and diagnosis, which enables efficient diagnosis of hEphA2-expressing cancer cells during positron emission tomography (PET) with improved targeting ability against hEphA2-expressing cancer cells, and uses of the method.

Description

Synthesis of human EphA2-specific monobody conjugated with a novel radioactive compound for cancer diagnosis and therapy and use thereof

The present invention relates to a novel cancer treatment radioactive compound and its use, and more particularly, to a method for preparing a human EphA2 specific monobody to which a novel cancer treatment and diagnosis radioactive compound is bound and its use.

Positron Emission Tomography (PET), also called positron emission tomography, is one of the nuclear medicine testing methods that use positron emission. A drug that combines a radioactive isotope that emits positrons is injected into the body and then is obtained through a positron emission tomography. This is a way to find out the distribution in the body by tracking. Through this, receptor images or metabolic images for cancer testing, heart disease, brain disease and brain function evaluation can also be obtained. Radioisotopes that emit positrons have a short half-life and are suitable for medical use. Among them, F-18 has a half-life of 110 minutes suitable for manufacturing and use of radiopharmaceuticals, and oxygen-18 concentrated water ([18O ]H ₂ O) can be easily mass-produced, specific activity is high, and the energy emitted is low, making it the most widely used nuclide in PET radiopharmaceuticals. The most representative radiopharmaceutical for PET, 2-[ ¹⁸ F]fluoro-D-glucose ([ ¹⁸ F] FDG), is a F-18-labeled glucose derivative that can image abnormalities in glucose metabolism in vivo and is used for tumor diagnosis. . However, in the case of the heart and brain, which generally consume a lot of glucose, there is a disadvantage that it is difficult to diagnose disease using [ ¹⁸ F]FDG, and in particular, the glucose intake is increased in various inflammatory tissues in which macrophages are activated, and thus it is imaged. [ ¹⁸ F]FDG is prescribed for tumor diagnosis, but since the inflamed area is also imaged, it is difficult to distinguish whether the abnormal area obtained by PET image is a tumor or inflammation, and accordingly, it may lead to an error in disease diagnosis. In this regard, Korean Patent Application Publication No. 2014-0113622 discloses a precursor of an ¹⁸ F-labeled PET radiopharmaceutical and a method of manufacturing the same.

In the case of the prior art, currently only ¹⁸ F FDG radiopharmaceuticals that can be used for tumor diagnosis are limited in use due to ingestion (muscles, inflammation, central nervous system) of non-tumor areas.

The present invention is to solve a number of problems including the above problems, and a method for preparing a human EphA2-specific monobody combined with a radioactive compound for novel cancer treatment and diagnosis capable of efficient imaging of cancer cells by improving targeting ability against hEphA2-expressing cancer cells And to provide the use thereof. However, these problems are exemplary, and the scope of the present invention is not limited thereby.

According to one aspect of the present invention, a novel radioactive compound having the structure of the following general formula 1 or an acceptable salt thereof is provided:

(일반식 1)

(General formula 1)

(In the above structural formula, E1 is an anti-hEphA2 monobody that specifically binds to human ephrin type A receptor 2 (hEphA2), L ₁ is a linker having at least two or more side chain reactive groups, and L ₂ is a hydrophobic imparting moiety. , L ₃ is an albumin binding moiety, R ₁ is a chelator, and R ₂ is a diagnostic or therapeutic radioactive isotope.)

According to another aspect of the present invention, there is provided a composition for molecular imaging for hEphA2, comprising the radioactive compound or an acceptable salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a composition for diagnosing or imaging cancer in which hEphA2 is overexpressed, comprising a radioactive compound or an acceptable salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a pharmaceutical composition for treating cancer comprising the radioactive compound or an acceptable salt thereof as an active ingredient.

As described above, the human EphA2-specific monobody conjugated with the novel cancer treatment and diagnostic radioactive compound of the present invention has improved targeting ability against hEphA2-expressing cancer cells, and thus a contrast agent for efficient diagnosis of hEphA2-expressing cancer cells during positron tomography (PET) and It can be used in the manufacture of cancer treatments. Of course, the scope of the present invention is not limited by these effects.

1 is a schematic diagram showing a method for synthesizing and labeling a precursor for a radioisotope-labeled anti-EphA2 monobody (hereinafter, abbreviated as'E1') according to an embodiment of the present invention.
2 is a graph analyzing the uptake capacity of hEphA2 overexpressing PC3 cells over time using radioactive isotope label E1 according to an embodiment of the present invention (*P <0.05).
3 is a PET image of a mouse tumor model prepared by injecting hEphA2 overexpressing PC3 cells and observing the uptake capacity after treatment with radioactive isotope label E1 according to an embodiment of the present invention (white arrow: tumor).
4 is a graph comparing organ intake values and tumor/organ intake ratios of a mouse tumor model according to treatment of radioisotope E1 according to an embodiment of the present invention.
FIG. 5 is a graph analyzing the intake values for each organ after 48 hours of a mouse tumor model according to treatment of the radioisotope label E1 according to an embodiment of the present invention.

Definition of Terms:

The term "human ephrin A type receptor 2 (hereinafter abbreviated as'hEphA2')" as used in this document belongs to the type A subgroup (EphA) of the ephrin receptor group proteins (Eph) in the protein-tyrosine kinase group receptor group. It is expressed on the cell surface as a membrane protein. Ephs are associated with embryonic nervous system development, stem cell differentiation, autophagy and tumor development processes. Eph is structurally composed of an ephrin binding domain, a cysteine-rich region, and an extracellular region composed of two FnIII-type repeats, and an intracellular region including a transmembrane domain and a kinase domain. Eph is divided into two groups, EphA and EphB, according to their affinity and amino acid similarity for ephrin ligand binding. EphA2 binds to the ephrin-A ligand. In particular, EphA2 is useful as a marker protein for early onset of gastric, lung, breast and prostate cancer.

As used herein, the term "hydrophobic imparting moiety" refers to naphs introduced for the purpose of increasing the stability in the body of radioactive compounds for imaging cancer lesions with PET or SPECT and enhancing the binding ability to target molecules. It means a moiety having a hydrophobic nucleus such as a yl group or a benzyl group.

As used herein, the term "albumin binding moiety" is a moiety for improving the circulation time of radiation therapy using radioactive compounds and is used to prolong the circulatory half-life of targeted radiation therapy (Cindy J. Choy et al., Theranostics , Vol. 7, Issue 7. 2017)

Detailed description of the invention:

According to one aspect of the present invention, a novel radioactive compound having the structure of the following general formula 1 or a pharmaceutically acceptable salt thereof is provided:

(일반식 1)

(General formula 1)

(In the above structural formula, E1 is an anti-hEphA2 monobody that specifically binds to human ephrin type A receptor 2 (hEphA2), L ₁ is a linker having at least two or more side chain reactive groups, and L ₂ is a hydrophobic imparting moiety. , L ₃ is an albumin binding moiety, R ₁ is a chelator, and R ₂ is a diagnostic or therapeutic radioactive isotope.)

및/또는

을 포함하는 링커일 수 있다. (상기 링커에서 상기 n은 1 내지 10 또는 1 내지 20의 정수이다). 상기 반응기는 아민기 또는 카르복실기일 수 있다. In the novel radioactive compound or a pharmaceutically acceptable salt thereof, the linker is

And/or

It may be a linker comprising a. (In the linker, n is an integer of 1 to 10 or 1 to 20). The reactor may be an amine group or a carboxyl group.

In the novel radioactive compound or a pharmaceutically acceptable salt thereof, the hydrophobic imparting moiety is

,

,

,

,

,

,

, 및

로 구성된 군으로부터 선택될 수 있다. 아울러, 상기 소수성 부여 모이어티에는 링커 골격(L₁)과의 일정 거리를 부여하기 위해서 라이신, 아르기닌, 글루타민, 글루탐산, 아스파라긴 또는 아르파르트산과 같은 염기성 또는 산성 아미노산이 부가될 수 있다. 이러한 염기성 또는 산성 아미노산의 구체예는 하기와 같다:

,

,

,

,

,

,

, And

It may be selected from the group consisting of. In addition, a basic or acidic amino acid such as lysine, arginine, glutamine, glutamic acid, asparagine, or arpartic acid may be added to the hydrophobic imparting moiety in order to impart a certain distance to the linker skeleton (L ₁ ). Specific examples of such basic or acidic amino acids are as follows:

,

, 및

,

,

, And

,

In the novel radioactive compound or a pharmaceutically acceptable salt thereof, the albumin binding moiety is

,

,

,

,

,

,

,

,

,

,

,

,

및

로 구성되는 군으로부터 선택될 수 있다.

,

,

,

,

,

,

,

,

,

,

,

,

And

It may be selected from the group consisting of.

In the novel radioactive compound or a pharmaceutically acceptable salt thereof, the chelator is DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DOTA-NCS, DOTA-NHS ester, DOTA-Bz-NCS, tris(t-bu)DOTA, HBED-CC-TFP ester, DTPA(Diethylene triamine penta aeetic acid), DO3A(1,4,7,10-tetraazacyclododecane-1,4,7- triacetic acid), NOTA(1,4,7-triazacyclononane-1,4,7-triacetic acid), NODAGA(1,4,7-Triazacyclononane,1-glutaric acid-4,7-acetic acid), TETA(1 ,4,8,11-tetraazacyclotetradecane- N,N',N",N"' -tetraacetic acid), TE3A(1,4,8,11-tetraazacyclotetradecane-1,4,8-triacetic acid), TE2A(1 ,4,8,11-Tetraazabicyclohexadecane-4,11-diacetic acid), PCTA(3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1,11,13-triene-3,6,9,- triacetic acid), cyclene, cyclam, and DFO (Deferrioxamine), and the radioactive isotopes are ¹⁸ F, ⁴⁴ Sc, ³² P, ⁶⁴ Cu, ⁶⁷ Cu, ⁹⁰ Cu, ⁶⁸ Ga, ^80m Br, ⁸⁵ Sr, ⁸⁹ Sr, ⁸⁶ Y, ⁹⁰ Y, ^99m Tc, ¹¹¹ In, ^114m In, ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ¹⁴⁹ Tb, ¹⁵² Tb, ¹⁵³ Sm, ¹⁶⁵ Dy, ¹⁶⁶ Ho, ¹⁶⁹ Er, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ²²³ Ra and ²²⁵ Ac It may be selected from the group consisting of.

In the novel radioactive compound or its acceptable salt, the bond may be an ester bond, an amide bond, an ether bond, a thioether bond, a thioester bond, or a disulfide bond.

According to another aspect of the present invention, there is provided a composition for molecular imaging for hEphA2, comprising the radioactive compound or a pharmaceutically acceptable salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a composition for diagnosing or imaging cancer in which hEphA2 is overexpressed, comprising a radioactive compound or a pharmaceutically acceptable salt thereof as an active ingredient.

According to another aspect of the present invention, there is provided a pharmaceutical composition for treating cancer comprising the radioactive compound or a pharmaceutically acceptable salt thereof as an active ingredient.

In the pharmaceutical composition for treating cancer, the cancer may be a cancer in which hEphA2 is overexpressed.

In the novel radioactive compound or a pharmaceutically acceptable salt thereof, the structure in which L1, L2, and L3 are connected may be described by the following specific structure, but is not limited thereto:

,

,

, 또는

, or

.

.

In addition to the above specific structure, the positions of L ₂ and L ₃ may be changed to other skeletal carbons in L ₁ , and the combination and length of the units in L ₁ may be variously adjusted.

Fn3 proteins that bind to various targets, that is, monobodies, have been developed and tested so far for clinical purposes such as diagnosis of diseases such as cancer and infection and development of therapeutic agents (Lipovsek, D., Protein Eng. Des. Sel. . 24(1-2): 3-9, 2011). In this regard, since the present inventors specifically bind with conventional hEphA2 and hEphA2 on the surface of human cells, human ephrin type A receptor 2 (hEphA2) that can be usefully used as a candidate material for a probe for in vivo diagnosis and treatment of tumors. A peptide having a human fibronectin domain III (Fn3) that specifically binds to and as a basic skeleton was developed (Korean Patent No. 1636882). The above patent document is incorporated by reference in this document.

The "pharmaceutically acceptable salt" is preferably a salt using an inorganic acid or an organic acid, more preferably a salt using an aliphatic such as methoxy, acetoxy, trifluoroacetoxy anion, chloride, bromide, iodide , Aromatic or aryl aliphatic carboxylate, nitrate, sulfate, phosphate, sulfonate, mesylate, besylate, tosylate, and the like, but are not limited thereto. In addition, acceptable salts of the invention F ^- also includes salts with ^-, Cl ^-, Br ^-, or I. However, the acceptable salt of the present invention is not limited thereto.

The effective amount of the pharmaceutical composition of the present invention may vary depending on the type of the affected part of the patient, the application site, the number of treatments, the treatment time, the formulation, the condition of the patient, the type of adjuvant, and the like. The amount used is not particularly limited, but may be 0.01 μg/kg/day to 10 mg/kg/day. The daily dose may be administered once a day, divided into 2-3 times a day at appropriate intervals, or intermittently administered at intervals of several days.

The pharmaceutical composition of the present invention may be contained in an amount of 0.1-100% by weight based on the total weight of the composition, and may further include suitable carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions. In addition, solid or liquid additives for preparation may be used in the preparation of pharmaceutical compositions. The additive for formulation may be either organic or inorganic. Examples of excipients include lactose, sucrose, sucrose, glucose, cornstarch, starch, talc, sorbit, crystalline cellulose, dextrin, kaolin, calcium carbonate, and silicon dioxide. As a binder, for example, polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, calcium citrate, And dextrin and pectin. Examples of the lubricant include magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil. Any colorant that is permitted to be added to pharmaceuticals can be used. These tablets and granules can be appropriately coated with a sugar coat, gelatin coating, or other necessary. In addition, preservatives, antioxidants, and the like may be added as necessary.

The pharmaceutical composition of the present invention can be prepared in any formulation conventionally prepared in the art (for example, Remington's Pharmaceutical Science, the latest edition; Mack Publishing Company, Easton PA), and the form of the formulation is not particularly limited. . These formulations are described in Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Blaug, Seymour), a formula generally known for all pharmaceutical chemistry.

The pharmaceutical composition of the present invention may be administered orally or parenterally, preferably parenteral administration by intravenous injection, subcutaneous injection, intracerebroventricular injection, intracerebrospinal fluid injection, intramuscular It can be administered by injection or intraperitoneal injection.

In the pharmaceutical composition, the anticancer drug is paclitaxel, 5-FU, docetaxel, tamoxin, anasterosol, carboplatin, topotecan, velotecan, imatinib, irinotecan, floxuridin, vinorelbine, gemcitabine , Leuprolide, flutamide, zoledronate, cisplatin, doxorubicin, vincristine, hydroxyurea, streptozotocin, and valubicin may be one or more selected from the group consisting of, but is not limited thereto, The anticancer protein may be a protein toxin, an antibody specific for a cancer antigen or a fragment of the antibody, a tumor suppressor protein, or an antiangiogenic factor. At this time, the protein toxin is a botulinum toxin (Botulinum toxin), Te tanuseu toxin (Tetanus toxin), Shiga toxin (Shiga toxin), diphtheria toxin (Diphtheria toxin, DT), ricin (ricin), Pseudomonas exotoxin (Pseudomonas exotoxin, PE ), Cytolysin A (ClyA), may be r-Gelonin. The tumor suppressor protein is a protein that suppresses the occurrence of tumors, typically VHL (von HippelLindau), APC (Adenomatous polyposis coli), CD95 (cluster of differentiation 95), ST5 (Suppression of tumorigenicity 5), YPEL3 (Yippee like 3). ), p53, ST7 (Suppression of tumorigenicity 7), and ST14 (Suppression of tumorigenicity 14). The anti-angiogenic factors include anti-VEGF antibody, angiostatin, endostatin, Kringle V domain of apolipoprotein, and the like.

Currently, research and development for the diagnosis of hEphA2-expressing cancer has not been conducted using radioactive isotopes except for diagnosis using optical equipment. In addition, radiopharmaceuticals that can be used for diagnosis of tumors have only ¹⁸ F FDG, and there are problems such as ingestion of non-tumor areas (muscles, inflammation, central nervous system). As a result of diligently making efforts to solve the above problems, the present inventors developed a fibronectin domain III basic skeleton radioactive compound targeting human EphA2 capable of efficient imaging of hEphA2 expressing cancer cells. The radioactive compound has improved targeting ability for hEphA2-expressing cancer cells, and thus it was confirmed that it can be used as a specific contrast medium for PET imaging, especially hEphA2-expressing cancer cells, and the present invention was completed.

Hereinafter, the present invention will be described in more detail through examples. However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various different forms, and the following embodiments make the disclosure of the present invention complete, and the scope of the invention to those of ordinary skill in the art. It is provided to fully inform you.

Disclosure material

2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N" -triacetic acid trihydrochloride ([p-SCN-Bn]-NOTA) used in the present invention was purchased from Futurechem and a buffer solution The NaHCO _{3 and} NH ₄ OAc used in the preparation were purchased from Sigma and used. The G-10 column used to separate the labeled E1 was purchased from GE healthcare, and the PC3 cells used in the experiment were purchased from ATCC and the mouse from Orient. Used.

Example 1: E1 ⁶⁴ Cu labeling method

The present inventors have purified E1 (Korean Patent No. 1636882, SEQ ID NO: 1) and 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane- N,N',N" -triacetic acid purified for ⁶⁴ Cu labeling NOTA-E1 was prepared by dissolving trihydrochloride ([p-SCN-Bn]-NOTA) in a 1.0 M NaHCO ₃ buffer (pH 9.2) at a ratio of 5:1 and reacting for 24 hours. split by a G-10 column and then was used to cover 0.1 M NH ₄ OAc buffer followed by the addition of NOTA-E1 in ⁶⁴ Cu binary dissolved in (pH 5.5) was allowed to react for 1 hour at 40 ℃. ⁶⁴ Cu the end cover is Labeled E1 was named " ⁶⁴ Cu-NOTA-E1" and separated through a G-10 column and used in subsequent experiments (FIG. 1).

Example 2: Cell line and cell culture

For cell culture, PC3 cells, a human prostate cancer cell line, were cultured using high-glucose RPMI medium to which 5% fetal bovine serum and 1% antibiotic were added.

Example 3: Cell uptake rate experiment

In the cell uptake experiment, PC3 cells (1x10 ⁶ cells) were dispensed into a 12 well plate 24 hours before the experiment and cultured for 24 hours. Thereafter, ⁶⁴ Cu-NOTA-E1 (0.74 MBq) prepared in Example 1 was treated and incubated for 1, 6 and 24 hours in a 37°C incubator, respectively. Finally, the cells were washed twice with DPBS, treated with trypsin, and then the content of ⁶⁴ Cu-NOTA-E1 in the cell culture medium and cells of each time group was measured with a gamma counter.

The result showed that the uptake rate increase as the ⁶⁴ Cu-NOTA-E1 only when the time has passed after the processing when ⁶⁴ Cu-NOTA-E1 uptake rate of PC3 cells After 17%, 24 over time to 77% ( Fig. 2).

Example 4: Tumor transplant mouse model PET image

In order to prepare a tumor transplant mouse model, a PC3 cell line was injected into the right shoulder of a nude mouse, and after about 3 weeks, a mouse with a tumor size of about 100 to 120 mm ³ was selected. Thereafter, the mouse was anesthetized for use in the experiment, and ⁶⁴ Cu-NOTA-E1 (7.4 MBq) according to an embodiment of the present invention was injected through the tail vein. Static microPET images were acquired at 1, 6, and 24 hours after the injection of the labeling compound to confirm the intake capacity in tumors, blood, and other organs.

As a result, after injection of ⁶⁴ Cu-NOTA-E1, the labeling compound of the present invention, the uptake rate in other organs decreased with time, but the uptake capacity in tumors was increased (FIG. 3 ). Therefore, it was confirmed that the ratio between the tumor and other organs gradually increased over time (FIG. 4).

Example 5: Body distribution experiment

For the in vivo distribution experiment of the tumor transplanted mouse model prepared according to an embodiment of the present invention, a PC3 cell line was injected into the right shoulder of a nude mouse, and after about 3 weeks, a mouse with a tumor size of about 100 to 120 mm ³ was selected. Next, ⁶⁴ Cu-NOTA-E1 (7.4 MBq) was injected into the tail vein of the mouse. After 48 hours, the mouse was sacrificed to extract tumors, blood and organs, and the intake rate of the extracted organs was measured with a gamma counter.

As a result, despite the passing of 48 hours, ⁶⁴ Cu-NOTA-E1 in the tumor showed an intake of about 4% ID/g (FIG. 5).

In conclusion, ⁶⁴ Cu-NOTA-E1, a labeling compound prepared according to an embodiment of the present invention, has improved targeting ability against hEphA2-expressing cancer cells, and thus can be used as a contrast medium for efficient diagnosis of hEphA2-expressing cancer cells during positron tomography. .

The present invention has been described with reference to the above-described embodiments, but these are merely exemplary, and those of ordinary skill in the art will appreciate that various modifications and equivalent other embodiments are possible therefrom. Therefore, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

Claims (12)

A novel radioactive compound having the structure of the following general formula 1 or an acceptable salt thereof is provided:

(General formula 1)
(In the above structural formula, E1 is an anti-hEphA2 monobody that specifically binds to human ephrin type A receptor 2 (hEphA2), L ₁ is a linker having at least two or more side chain reactive groups, and L ₂ is a hydrophobic imparting moiety. , L ₃ is an albumin binding moiety, R ₁ is a chelator, and R ₂ is a diagnostic or therapeutic radioactive isotope.) The method of claim 1,
The linker is

And/or

A linker comprising, a novel radioactive compound or an acceptable salt thereof.
(In the linker, n is an integer of 1 to 10 or 1 to 20). The method of claim 1,
The reactor is an amine group or a carboxyl group, a novel radioactive compound or an acceptable salt thereof. The method of claim 1,
The hydrophobic imparting moiety is

,

,

,

,

,

,

, And

A novel radioactive compound or an acceptable salt thereof selected from the group consisting of. The method of claim 1,
The albumin binding moiety is

,

,

,

,

,

,

,

,

,

,

,

,

And

A novel radioactive compound selected from the group consisting of or an acceptable salt thereof. The method of claim 1,
The chelator is DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DOTA-NCS, DOTA-NHS ester, DOTA-Bz-NCS, tris(t-bu)DOTA , HBED-CC-TFP ester, DTPA (Diethylene triamine penta aeetic acid), DO3A(1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid), NOTA(1,4,7-triazacyclononane-1 ,4,7-triacetic acid), NODAGA(1,4,7-Triazacyclononane,1-glutaric acid-4,7-acetic acid), TETA(1,4,8,11-tetraazacyclotetradecane- N,N',N ",N"' -tetraacetic acid), TE3A(1,4,8,11-tetraazacyclotetradecane-1,4,8-triacetic acid), TE2A(1,4,8,11-Tetraazabicyclohexadecane-4,11-diacetic acid ), PCTA(3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1,11,13-triene-3,6,9,-triacetic acid), Cyclen, cyclam And DFO (Deferrioxamine) selected from the group consisting of, a novel radioactive compound or an acceptable salt thereof. The method of claim 1,
The radioactive isotopes are ¹⁸ F, ⁴⁴ Sc, ³² P, ⁶⁴ Cu, ⁶⁷ Cu, ⁹⁰ Cu, ⁶⁸ Ga, ^80m Br, ⁸⁵ Sr, ⁸⁹ Sr, ⁸⁶ Y, ⁹⁰ Y, ^99m Tc, ¹¹¹ In, ^114m In, ^{Consisting of 123} I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ¹⁴⁹ Tb, ¹⁵² Tb, ¹⁵³ Sm, ¹⁶⁵ Dy, ¹⁶⁶ Ho, ¹⁶⁹ Er, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁸ Au, ²²³ Ra and ²²⁵ Ac A novel radioactive compound or an acceptable salt thereof selected from the group. The method of claim 1,
The bond is an ester bond, an amide bond, an ether bond, a thioether bond, a thioester bond, or a disulfide bond, a novel radioactive compound or an acceptable salt thereof. A composition for molecular imaging for hEphA2, comprising the radioactive compound of any one of claims 1 to 8 or an acceptable salt thereof as an active ingredient. A composition for diagnosing or imaging cancer in which hEphA2 is overexpressed, comprising the radioactive compound of any one of claims 1 to 8 or an acceptable salt thereof as an active ingredient. A pharmaceutical composition for cancer treatment, comprising the radioactive compound of any one of claims 1 to 8 or an acceptable salt thereof as an active ingredient. The method of claim 11,
The cancer is hEphA2 overexpressed cancer, a pharmaceutical composition for cancer treatment.

Images