JPH0454165A - New heterocyclic compound - Google Patents

Abstract

NEW MATERIAL:A heterocyclic group-bound carbamoylmethyliminodiacetic acid expressed by the formula (R is heterocyclic group selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, pyrazyl and 6purinyl). EXAMPLE:4-Pyridylcarbamoylmethyliminodiacetic acid. USE:An ingredient of radiodiagnostic agents for detecting cancer and abscessed sites. PREPARATION:Nitrilotriacetic acid is reacted with acetic anhydride in pyridine to provide anhydrous nitrilotriacetic acid. A heterocyclic compound is then added and condensed to afford the compound expressed by the formula. A <99m>TC-labeled complex formed from the compound expressed by the formula and technetium 99m(<99m>TC) has quick clearance in blood and is capable of exhibiting high accumulating properties in cancer and abscessed sites and can be detected in a short time.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Fields] The present invention relates to a novel compound, a heterocyclic group bonding force, rubamoylmethyliminodiacetic acid, and a combination of this compound and technetium 99m.
99m7C labeled complex formed from (99°Tc),
The present invention relates to a composition comprising the compound and a pertechnetate reducing agent for preparing the complex, and a radioactive diagnostic agent for detecting cancer and abscess sites containing the complex as an active ingredient.

[Prior Art] Conventionally, radioactive diagnostic agents such as gallium citrate (67Ga) and thallium chloride (1Tl) have been widely used clinically for the purpose of nuclear medicine dynamic examination of cancer.

[Problems to be Solved by the Invention] Although the above-mentioned known diagnostic agents have the property of accumulating in cancer, they have the disadvantage that their selectivity is low and it is difficult to obtain clear scintigraphic images.

Therefore, it has been desired to develop a cancer diagnostic agent complexed with Tc, which is the most commonly used nuclide for radiodiagnostic agents administered into the body.

An object of the present invention is to provide a novel technetium complex that enables diagnosis of cancer and abscess sites.

Means for Solving Problem C] It is well known that cancer and abscess tissues have more anionic residues such as acidic mucopolysaccharide than normal sites, and are inclined to the acidic side. Therefore, we attempted to prepare a complex with cationic residues in order to interact with these anionic residues and temporarily accumulate them selectively in target tissues. Also,
As pi( decreases, the hydrophilicity of the complex increases, and cationic residues are also required to suppress the return of the complex from the target tissue.

The present inventors investigated 99°Tc complexes of ligands having a heterocyclic ring for the purpose of developing excellent cancer diagnostic agents.
99mT exhibits extremely superior properties compared to conventional diagnostic agents
The inventors discovered a c-labeled cancer diagnostic marker and completed the present invention. This complex has the advantage of rapid blood clearance, high accumulation in cancer and abscesses, and the ability to detect cancer and abscess sites within a short period of time after administration.

The present invention will be explained in detail below.

The present invention is based on a general formula.

(In the formula, R is a 2-pyridyl group or a 3-pyridyl group.

4-pyridyl group, 2-pyrimidyl group, pyrazyl group and 6
- a heterocyclic group selected from the group consisting of purinyl group). That is, the compound of the present invention is specifically 2-pyridylmethyliminodiacetic acid.

3-Pyridylrubamoylmethyliminodiacetic acid.

4-Pyridylcarbamoylmethyliminodiacetic acid.

2-pyrimidyl rubbermoylmethyliminodiacetic acid.

biradyl, rubamoylmethyliminodiacetic acid and 6-brinylcarpamoylmethyliminodiacetic acid.

The heterocyclic group bonding force of the present invention is obtained by synthesizing nitrilotriacetic anhydride in the presence of acetic anhydride in pyridine using nitrilotriacetic acid as a raw material, as shown in Example 1 herein, for example. This solution contains heterocyclic compounds, namely 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, 2-aminopyrimidine,
It can be produced by adding aminopyrazine or adenine (also known as 6-aminobulin) and condensing it.

As described above, the novel compound of the present invention is a compound in which nitrilotriacetic acid, which is a chelate ligand, is condensed with a heterocyclic compound such as pyridine, pyrimidine, or purine to which an amino group is bonded.
9h Chium! T formed from 19mf Tc)
The c-labeled complexes have been found to be particularly useful in diagnosing cancer and abscess sites. Until now, technetium 99111 has never been used as a diagnostic agent for cancer or abscess sites.

Therefore, the present invention also provides a Tc-labeled complex formed from 99mTc9m and 99mTc9m and 99mTc9m.

Of course, it is to be understood that complexes of the present invention having substituted analogues of the heterocyclic group shown in the above formula or related heterocyclic groups other than the heterocyclic group having similar properties can also form part of the present invention. .

99°Tc has a short half-life of about 6 hours, and in the experiment on mice described below, the half-life of 99°Tc is 8 hours after administration of the complex of the present invention.
It was found that accumulation in the body was low since 0-85% was transferred to the bladder and urine. In addition, as long as the effective dose was tested intravenously in mice, no acute toxicity of the complex of the present invention was observed.

The distribution of the 99m7c-labeled complex of the present invention in the body after administration was investigated by intravenously injecting it into tumor-bearing mice or abscess-bearing mice, removing blood, urine, tissues, and organs over time and measuring their radioactivity. For both complexes, the cancer or abscess/blood ratio was 1.0 or more in tumor-bearing mice 1 hour after administration and in abscess-bearing mice 30 minutes after administration, and 1 hour after administration, there was a significant increase in cancer or abscess sites. Accumulation was observed. This fact is confirmed by the results of scintigraphy after administering the complex of the present invention to tumor-bearing mice and abscess-bearing mice (Figures 1 and 2).
It was also supported by At this time, the complex of the present invention is administered for 1 day after administration.
The fact that it accumulates approximately 85% in the bladder and urine, and 5-7% in the intestines, liver, and kidneys at the same time, indicates that it is easily excreted from the body and that its clearance in the blood is fast.

Therefore, the 991″Tc-labeled complex of the present invention can be prepared from the conventionally known gallium citrate (67Ga), thallium chloride (201″
Compared to radioactive diagnostic agents such as Tl), it shows high accumulation or selectivity at cancer and abscess sites, and can be tested in about 45 minutes for cancer and about 20 minutes for abscess, allowing for rapid diagnosis. possible.

The Tc-labeled complex of the present invention can be easily prepared by mixing the heterocyclic group binding force of the present invention, rubamoylmethyliminodiacetic acid, pertechnetate, and a pertechnetate reducing agent. Accordingly, the present invention further provides a composition comprising a heterocyclic group-binding group rubamoylmethyliminodiacetic acid and a pertechnetate reducing agent for preparing a Tc-labeled complex.

The term "pertechnetate reducing agent" as used herein refers to an agent that reduces pertechnetate to a low valence state that is favorable for the formation of a strong chelate compound, and generally water-soluble reducing agents are used. . In preparing the composition of the present invention,
The composition may be in the form of a solution or a lyophilized product or a powder mixture. Furthermore, a substance having an antioxidant effect, such as ascorbic acid or erythorbic acid, may be added as a stabilizer to the composition of the present invention, and the addition of such a stabilizer is rather preferable. Furthermore, the addition of tonicity agents such as sodium chloride, preservatives such as benzyl alcohol, or acids and bases for pH adjustment does not in any way interfere with the purpose of the compositions of the invention. The water-soluble reducing agent can be added to the composition of the present invention by adding a water-soluble compound having a reducing ability directly into the composition, or by adding a metal ion having a reducing ability to a cation exchange resin. It is also possible to add it to the composition in the form of adsorption. As the water-soluble reducing agent referred to herein, any pharmaceutically acceptable reducing agent may be used, with preference given to stannous salts and sodium dinitionite. A stannous salt is a salt formed by divalent tin, and specifically includes, for example, halide ions such as chloride ion and fluoride ion, inorganic acid residue ions such as sulfate ion and nitrate ion; tartaric acid ion, acetate ion, citrate ion, and other organic acid residue ions.

The present invention further provides a radioactive diagnostic agent for detecting cancer and abscess sites, which contains the 99rATC-labeled complex of the present invention as an active ingredient. The new radiodiagnosis GM agent of the present invention comprises adding an effective amount of an aqueous solution of the composition of the present invention containing Tc in the form of pertechnetate, an acid, a base, a buffer solution, and a stabilizer for adjusting the pH of the aqueous solution. Appropriate additives such as tonicity agents and preservatives can be included. The radioactivity of 99°Tc that is brought into contact during the examination is optional, but it must be such a radioactivity that sufficient information can be obtained when carrying out the intended nuclear medicine diagnosis, and that the patient can be exposed to radiation. It goes without saying that it is desirable to keep the radioactivity as low as possible, but lθ~800
MBq is common.

Regarding the administration method, intravenous administration or intraarterial administration is performed, but after administration of the radiodiagnostic agent of the present invention,
Any method of administration that is advantageous for the expression of the activity may be used, and other methods may also be used.

After administration, it can be effectively used for nuclear medicine diagnosis of cancer and abscess sites by continuously or periodically performing imaging or radioactivity measurement with a gamma camera or scintillation scanner at a time appropriate for the purpose of diagnosis. be able to.

Hereinafter, the present invention will be described in detail with reference to Examples.

Example 1 1) Synthesis of 4-pyridyl-rubamoylmethyliminodiacetic acid Nitrilotriacetic acid (117
(M, W, 191.14), add about 20 ml of anhydrous pyridine, and suspend. Since this is an anhydrous reaction, care must be taken to avoid contamination with water.

Jimroth.

Attach the silica gel tube and warm it in an oil bath. Next, 1.25 ml of acetic anhydride was added, and the mixture was refluxed for 1 hour with stirring in an oil bath at 100°C to synthesize an anhydride of NTA. After cooling, equimolar 4-aminopyridine (M, WB2, 12) with NTA 0.
Add 98 g directly and wash in with a small amount of anhydrous pyridine.

Thereafter, the mixture was refluxed with stirring in an IH°C oil bath for 1 hour. After cooling and suction filtration, the solvent is distilled off. The residue is purified by passing through a LH20 column (solvent: methanol:water (1:1)). When the UV-absorbing fraction was made weakly acidic, colorless crystals with m and p of 218-221°C were obtained.

Anal, Cs1cd, ClIH13N 30
: C, 49, 44; H, 4, 90; N, 15
．． 72. Found: c, 49.44; H,
4,90; N, 15.72°MS: 268 (M+1
).

2) Synthesis of 3-pyridylmethyliminodiacetic acid Nitrilotriacetic acid (II) was placed in a 100 ml eggplant flask.
T person) (M, W, 191.14) Add 2.00 g, add about 20 ml of anhydrous pyridine, and suspend. Since this is an anhydrous reaction, care must be taken to avoid contamination with water.

Jimroth.

Attach the silica gel tube and warm it in an oil bath. Next, 1.25 ml of acetic anhydride was added, and the mixture was refluxed for 1 hour with stirring in an oil bath at 100°C to synthesize an anhydride of NTA. After cooling, 3-aminopyridine (M, WB2, 12) in an equimolar amount as NTA 0.
Add 98 g directly and wash in with a small amount of anhydrous pyridine.

Thereafter, 1G (refluxed for 1 hour with stirring in an oil bath at 1°C. After cooling and suction filtration, the solvent was distilled off. Water was added, and the precipitated crude crystals were purified by recrystallization from water-methanol. As a result, colorless crystals with m, p, and 225-228°C were obtained. Anal, Caled, C11H13N O:C
,49,44;H,4,90;N, 15.72°Fo
und: C, 49,96; H, 4,96; N, L
5.72, MS +258 [M+1).

3) Synthesis of 2-pyridylmethyliminodiacetic acid Nitrilotriacetic acid CNT^ in a 100 ml eggplant flask
) (i W, 191.14) Add 2.00 g,
Add approximately 20 ml of anhydrous pyridine and suspend. Since this is an anhydrous reaction, care must be taken to avoid contamination with water. Jimroth.

Attach the silica gel tube and warm it in an oil bath. Next, 125 ml of acetic anhydride was added and the mixture was refluxed for 1 hour with stirring in an oil bath at 100°C to synthesize an anhydride of NTA. After cooling, equimolar 2-aminopyridine (M, W94, 12) with NTA 0.9
Add 8 g directly and wash in with a small amount of anhydrous pyridine. Thereafter, the mixture was stirred and refluxed for 1 hour in an oil bath at 100°C. After cooling and suction filtration, the solvent is distilled off. Residue LH20
Purify through a column (solvent: methanol/water (111)'). IN the fraction with UV absorption
When made weakly acidic with HCffi, Ii, p, 198~
Colorless crystals at 202°C were obtained. Ana 1. Cal
cd.

CHN O: C, 49,44; H, 4,90; N.

+1 13 3 5 15.72. Found: C, 49, 24; H, 4
, 71; N, 16.03.

M S: 268 (M+ll.

4) Synthesis of 2-pyrimidyl-rubamoylmethyliminodiacetic acid Add nitrilotriacetic acid (N
TA) (M, W, 191.14) 2. Go
Add about 20 ml of anhydrous pyridine and suspend. Since this is an anhydrous reaction, care must be taken to avoid contamination with water. Attach a silica gel tube with a Dimroth and warm it in an oil bath.

Next, 125 ml of acetic anhydride was added, and 125 ml of acetic anhydride was added, and the
Reflux for a period of time to synthesize anhydride of NTA. After cooling, NT
A and equimolar 2-aminopyrimidine (M, W, 95.
10) Add 0.99g directly and wash in with a small amount of anhydrous pyridine.

Thereafter, the mixture is refluxed for 1 hour in an oil bath at 100°C. After cooling and suction filtration, the solvent is distilled off. The residue is purified by passing through a LH20 column (solvent: methanol:water (1:I)). The UV-absorbing fractions are made slightly acidic with 1N HCl and concentrated. When a small amount of alcohol was added to the solution, colorless crystals with m and p of 213-215°C were obtained. Anal, Ca1c+1. CHN O:C.

44.78; H, 4,51; N, 2[1,89. F
ound: C, 44, 75; H, 4, 5B, N, 2
0.72°MS: 269 (Mal) 5) Synthesis of biradyl-rubamoylmethyliminodiacetic acid In a 100 ml eggplant flask, add nitrilotriacetic acid (NT
A) (M, W, 191.14) Add 2.00 g, add about 20 ml of anhydrous pyridine, and suspend. Since this is an anhydrous reaction, be careful not to get moisture in it. silica gel tube.

Heat the Dimroth in an oil bath. Next, add 1 acetic anhydride
Add 25ml and reflux for 1 hour in an oil bath at 100°C.
Synthesize the anhydride of A. After cooling, 0.99 g of aminopyrazine (M, W, 95.12) equimolar to NTA is added directly and washed in with a small amount of anhydrous pyridine. After that, 1
Reflux for 1 hour in an oil bath at B°C. After cooling and suction filtration, the solvent is distilled off. Dissolve the residue in a small amount of water and
CI! When made weakly acidic, crystals precipitated. When the crystals were recrystallized from water-methanol, colorless crystals with an ff of 1.9220 to 221°C were obtained. ^nal, C3ledCHN O:
C, 44,78; H, 4,51; N.

20.89, Fo+ud:C,44,65;H
, 4,62; N, 20.89.

MS: 269 (Mal).

*If you repeat reconnection, it will be a little bit 1. p has gone up.

6) Synthesis of 6-brinylcarpamoylmethyliminodiacetic acid Add nitrilotriacetic acid (NTA) to a 100ml eggplant flask.
) (M, W, 191.14), add about 20 ml of anhydrous pyridine, and suspend. Since this is an anhydrous reaction, be careful not to get moisture in it. silica gel tube.

Heat the Dimroth in an oil bath. Next, add 1 acetic anhydride
．． Add 25ml and reflux for 1 hour in an oil bath at 100°C.
Synthesize TA anhydride. After cooling, 1.41 g of adenine (M, W, 135.13) equimolar to NTA are added directly. In order to dissolve as much adenine as possible, anhydrous pyridine as a solvent is further added, and the mixture is refluxed for 1 hour in an oil bath at 100°C (all adenine does not dissolve). After cooling, unreacted adenine is removed by suction filtration, and the solvent is distilled off. The residue was transferred to an LH20 column (solvent; methanol:water (
1:1)) to purify. When the UV-absorbing fraction is made weakly acidic with IN HCI, m, p,
A scaly colorless crystal having a temperature of 212 to 213°C was obtained. Aoi
l, Calcd, C11H12N605: C.

42.116; H, 3,92; N, 27.26,
Found: C, 42, 81; H, 3, 98, N,
27.26°MS・309 (Mal) Example 2 Preparation of composition for labeling 99mTC-labeled complex Heterocyclic group binding strength of 0,051J Rubamoylmethyliminodiacetic acid aqueous solution (
(Using water for injection) I ml (pH 7,4) and 20 μl/ml of stannous chloride as a pertechnetate reducing agent.
(0,IN HCj! solution) was added in an amount of 0.1 ml, and then passed through a 122μ membrane filter to obtain the desired composition.

Example 3 Preparation of a radioactive diagnostic agent containing a 990TC labeled complex as an active ingredient To 1.0 ml of the composition obtained in Example 2, add 2 to 3 ml of pertechnetate-99m-r C solution (300 to 5 HIJB
ql was added and then passed through a 022μ membrane filter to obtain the desired radioactive diagnostic agent.

Example 4 Properties of a radioactive diagnostic agent containing a 990TC labeled complex as an active ingredient In order to investigate the labeling rate of the 99mTc complex contained in the radioactive diagnostic agent obtained in Example 3, (1) thin layer chromatography (2) electrophoresis was conducted. and scanned with a radiochromatography scanner.

(1) Thin layer chromatography Using a silica gel thin layer plate, the reaction was developed with 70% acetonitrile water as a developing solvent. When developed with this solvent for 9 m, a radioactive peak was observed at the upper limit for pertechnetate and at the origin for Tc tin colloid.

In the complex solution obtained in Example 3, most of the radioactivity peaks were observed around R10.8 (Table 1). Partial R [value 0.3
A radioactivity peak characteristic of NTA derivatives was faintly detected near 4. Also, free 99mTc.

The amount of oxidation and technetium oxide was small, and it was judged that it did not interfere with the properties of the diagnostic agent of the present invention as a diagnostic agent.

table 4-pyridylcarbamoyl O)5 90, 4 methyliminodiacetic acid 3-pyridylcarbamoyl 0.111 methyliminodiacetic acid 2-pyridylcarbamoyl 0.83 methyliminodiacetic acid 2-pyrimidylcarbamoyl methyliminodiacetic acid 2-Viradylcarbamoyl 0.77 88.6 methyliminodiacetic acid 6-purinylcarbamoyl 0.89 methyliminodiacetic acid (2) Electrophoresis Electrophoresis was performed under the following conditions.

Indicator: filter paper Electrophoresis liquid.

Acetate buffer (pH 4,8) Running conditions: 6004, 30 minutes The results of filter paper electrophoresis are shown in Table 2.

Surface coordination Child 4-Pyridylcarbamoylmethyliminodiacetic acid mobility (an) One side 0.41 3-Pyridylcarbamoylmethyliminodiacetic acid One side 043 2-Pyridylcarbamoylmethyliminodiacetic acid One side 0.86 2-Pyrimidium 1.29 methyliminodiacetic acid 2-biradylcarbamoylmethyliminodiacetic acid 1 side 1.57 lopurinylcarbamoylmethyliminodiacetic acid 1 side 1.14 As a result, there is one radioactive band at 9 m near the -constraint Law. A band was detected and the presence of free TeO2 (moved to the - side 50) was ruled out. In addition, it is suspected that a complex of NTA is formed when the compound is hydrolyzed, but
Since the complex migrated to 4.5 an on one side, its existence could also be denied.

Example 5 This example shows the case of a 99mTc-labeled complex in which the heterocyclic-containing ligand is 4-pyridyl-rubamoylmethyliminodiacetic acid. Similar results to those shown below were obtained in the case of a complex consisting of iminodiacetic acid.

0.15 ml (37 M [lq)] of the radiodiagnostic agent obtained in Example 3 was administered through the tail vein to an ICR male mouse (weighing approximately 35 g) in which Ehrlich ascites carcinoma was implanted in the thigh, and blood was administered over time. and urine were collected, tissues and organs were removed, and the radioactivity in each sample was measured. The results are shown in Table-3.

Elapsed time (min 1 ml of blood 1 g of muscle 1 g of cancer Salivary gland lung gastrointestinal liver kidney (left) Kidney (right) Cancer/muscle cancer/blood table -3 112% 0.55% 0, 39 0.22 0.87 Q.58 G , 18 0.14 0, 07 0.07 0, 19 0.13 1.69 1.50 2, 03 1.88 1.86 1,10 1, 12 0.74 2.23 2.63 1.05 As can be seen from the table, 99111TC-4-pyridi/L
The cancer/blood ratio of the carbamoylmethyliminodiacetic acid complex was approximately IO 1 hour after administration, and it was observed that it accumulated in cancer 1 hour after administration, confirming that it is extremely useful for nuclear medicine diagnostic purposes.

In the examples, the case of a 99alTc-labeled complex in which the heterocyclic-containing ligand is 4-pyridylmethyliminodiacetic acid is shown, but other five types of the present invention's heterocyclic group-binding Similar results to those shown below were obtained in the case of a complex consisting of methyliminodiacetic acid.

Liquid paraffin/turpentine oil (1/l) 0.05 m
The radiodiagnostic agent obtained in Example 3 was administered to male ICR mice (weighing approximately 35 g) in which abscesses were induced by administering 0.1 to the radiodiagnostic agent obtained in Example 3.
1 ml was administered through the tail vein, blood and urine were collected over time, tissues and organs were extracted, and the radioactivity in each sample was measured. The results are shown in Table 4.

Table -4 1,16N 0.39 1.33 0.15 0.07 0.14 2.46 1.53 1.12 72.55 3.41 1.15 0.58% 0.98 0.08 0 .05 0.13 2.02 1.41 G, 98 83.05 Elapsed time (fflin) 1 ml of blood 1 g of muscle 1 g of abscess Salivary gland lung gastrointestinal liver kidney (left) Kidney (right) Bladder + urine abscess/muscle abscess/blood table As can be seen, the abscess/blood ratio of 99111TC-4-pyridyl-rubamoylmethyliminodiacetic acid complex was 1.0 or more 30 minutes after administration, indicating that it accumulated in abscesses within a short period of time after administration. It was confirmed that it is extremely useful for nuclear medicine diagnostic purposes.

Example 7 The radioactive diagnostic agent obtained in Example 3 was intravenously injected into a mouse in which the Ehrlich ascites carcinoma shown in Example 5 was transplanted into the right upper limb, and the time course was monitored using a gamma camera equipped with a parallel collimator for 45 minutes after administration. A scintigram was obtained (Fig. 1).

As a result, cancer was visualized approximately 20 minutes after administration of the complex, and became more clearly visualized 30 minutes later. From this result, it was confirmed that heavy punishment is useful as a cancer diagnostic agent. Similar results were obtained in the case of 9m-coordinated Tc complexes having five other types of heterocycles.

Example 8 The radioactive diagnostic agent obtained in Example 3 was intravenously injected into a mouse in which an abscess had been induced by the method shown in Example 6, and a scintigram was obtained 20 minutes after administration in the same manner as in Example 7. Figure 2).

As a result, the abscess induced in the right upper limb was visualized approximately 1 day after administration.
It was recognized from 0 minutes and was more clearly visualized from 20 minutes later. From this result, it was confirmed that heavy punishment is useful as an abscess diagnostic agent. Similar results were obtained for 99rATC complexes of other five types of heterocycle-containing ligands.

[Effects of the Invention] The 9911IITc-labeled complex of the present invention has rapid blood clearance, shows high accumulation at cancer and abscess sites, and can detect cancer and abscess within a short time after administration. It is useful as a site diagnostic agent.

[Brief explanation of drawings]

9m FIG. 1 is a photograph showing a scintigram 45 minutes after administration of a radiodiagnostic agent containing Tc-4-pyridylmethyliminodiacetic acid as an active ingredient to tumor-bearing mice. 9m FIG. 2 is a photograph showing a scintigram 20 minutes after the administration of a radiodiagnostic agent containing Tc 4-pyridyl-rubamoylmethyliminodiacetic acid as an active ingredient to an abscess-bearing mouse. End figure unillustrated procedure amendment 8, content of amendment [C, 49, 44:
August 1990 mortar

Claims (6)

[Claims] (1) General formula: ▲ Numerical formula, chemical formula, table, etc. carbamoylmethyliminodiacetic acid bound to a heterocyclic group, which is a heterocyclic group selected from the group consisting of: (2) Heterocyclic group-bonded carbamoylmethyliminodiacetic acid according to claim 1 and technetium 99m (^9^9^mT
c)^9^9^mTc-labeled complex formed from and. (3) A composition for preparing the ^9^9^mTc-labeled complex according to claim 2, which comprises the heterocyclic group-bonded carbamoylmethyliminodiacetic acid according to claim 1 and the pertechnetate reducing agent. A composition consisting of. (4) The composition according to claim 3, wherein the pertechnetate reducing agent is a stannous salt or sodium dithionite. (5) The composition according to claim 4, wherein the stannous salt is stannous chloride. (6) A radioactive diagnostic agent for detecting cancer and abscess sites, comprising the ^9^9^mTc labeled complex according to claim 2 as an active ingredient.