GB2101118A - Technetium (99m)-labeled compound and process for production of said compound - Google Patents
Technetium (99m)-labeled compound and process for production of said compound Download PDFInfo
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- GB2101118A GB2101118A GB08212520A GB8212520A GB2101118A GB 2101118 A GB2101118 A GB 2101118A GB 08212520 A GB08212520 A GB 08212520A GB 8212520 A GB8212520 A GB 8212520A GB 2101118 A GB2101118 A GB 2101118A
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- 99mtc
- isonicotinylhydrazine
- isonicotinoylhydrazine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/86—Hydrazides; Thio or imino analogues thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
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- Medicinal Chemistry (AREA)
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Abstract
<99m>Tc-labeled isonicotinoylhydrazine, a process for producing said compound, and an agent for use in the diagnosis of malignancy, containing said compound as a major component are described. This compound is prepared by reducing a pertechnetate (99m) with a reducing agent in an isonicotinoylhydrazine-containing solution under acidic, alkaline or neutral conditions.
Description
SPECIFICATION
Technetium (99m)-labeled compound and process for production of said compound
The present invention relates to a novel technetium (99m)-labeled compound. More particularly it relates to technetium (99m)-labeled isonicotinoylhydrazine (hereinafter referred to as "99mTC isoniazid"), a process for the production of 99mTc isoniazid, and a novel agent for diagnosis of malignancy, composed mainly of said 99mTc isoniazid.
A radioactive gallium salt of citric acid (hereinafter referred to as "67Ga citrate") has heretofore been used in the diagnosis of malignancy. Although this 67Ga citrate is useful as a scanning agent since it has a high affinity to various carcinomata, it is undesirable because it has a high affinity not only with respect to malignancy but also to other inflammatory tissues, serious difficulties are encountered in distinguishing between them. Further more 67Ga citrate is undesirable because it can only be administered in small amounts because of dangers resulting from the exposure of the interior of body to 67Ga and no satisfactory scintillographic images can be obtained. Furthermore, production cost is relatively high.
In view of the above described problems, 67Ga citrate is not considered suitable for use in the routine examination.
In recent years, technetium (99m) (hereinafter indicated as "99mTc") has received increasing attention as a very useful radioactive agent for use in the diagnosis of malignancy. The reasons for this are: (1 ) the time during which the organs are exposed to radiation can be greatly reduced since 99mTc has a short half-life of 6 hours, and (2) since 99mTc provides a sufficient tissue-permeation force because of its high y-radiation energy (140 KeV and, furthermore, it emits y-rays without the emission of B-radiation rays, in vivo examination can be carried out without exposing patients to hazardous amounts of radiation.
At present, nuclear medical diagnosis using 99mTc in the form of composites of various ligands, and 99mTc is widely used by taking advantage of properties of these ligands in diagnosis for functions or shapes of most of main organs in human body, such as cerebrum, spinal cord cavity, thyroid gland, lung, heart, liver, hepatobiliary pathway, spleen, kidney, bones, placenta, salivary glands and the like. However, the utility of 99mac in the field of tumor diagnosis has been limited in spite of its excellent physico-chemical properties.
More specifically, 99mTc is practically used only in the diagnosis of cerebral tumors in the form of a free pertechnetate solution based on the distribution of 99mTc in the brain when the blood brain barrier is ruptured due to the cerebral tumor, or in the diagnosis of bone tumors or bone metastatic lesions by bone scanning using a composite of 99mTc and a ligand having bone accumulation such as a pyrophosphate or methylene diphosphonate, or in the negative imaging as a space-occupying lesion of liver cancer or liver metastatic lesion by liver scanning based on the reticuloendothelial phagocyte function using a 99mTc labeled colloid such as phytate or sulfur colloid. That is, at present, a tumor imaging agent based on the affinity to a tumor comprising a 99mTc-labeled ligand has not been practically used.
In such in vivo examinations, therefore, it is desirable to use those compounds prepared by labeling with 99mTe which is believed ideal for use in the examinations. However, 99mTc-labeled compounds capable of providing satisfactory results in this field are practically unknown. Radiopharmaceutical chelates including technetium-99m are disclosed in U.S. Patent 4,017,596.
An object of the invention is to provide a 99mTc-labeled compound which is free from the above-described defects.
Another object of the invention is to provide an agent for use in diagnosis of malignancy.
A further object of the invention is to provide a process for producing a 99mTc-labeled compound.
Other objects and advantages of this invention will become apparent from the following detailed description.
The present invention, therefore, provides: (1 ) 99mTc-labeled isonicotinoylhydrazine;
(2) a process for preparing 99mTc-labeled isonicotinoylhydrazine which comprises reducing a pertechnetate (99m) with a reducing agent in an isonicotinoylhydrazine-containing solution under acidic, alkaline or neutral conditions; and
(3) an agent for use in diagnosis of malignancy, which contains 99mTc-labeled isonicotinoylhydrazine as a major component.
The accompanying drawing is a photograph obtained by an anterior imaging study in rat taken by a y-camera after administration of a 99mTc-isoniazid composite solution.
99etc isoniazid of the invention is very effective as an agent for use in diagnosis, due to the above-described excellent properties of 99mTc. Particularly, it is useful as a scanning agent for the examination of a tumor because the tumor/tissue ratio is extremely high, as shown in the example as described hereinafter, and, furthermore, accumulation onto a transferred tumor can be easily distinguished.
When 99mute isoniazid is employed as a tumor scanning agent, it can be used in an amount of from 1 to 100 mCi, preferably from 5 to 25 mCi, based on the weight of a living body. The use of 99mTc isoniazid in such amounts makes it possible to obtain sufficient tissue-permeation force in in vivo scanning, to greatly reduce the amount of radiation to which a patient is to be exposed, and to obtain satisfactory scintillographic images.
With regard to the toxicity of 99mTc isoniazid, it is impossible to administer 99mTc in such large amounts that the toxicity is caused to appear. It has been confirmed that as long as 99mTc isoniazid is used within the above-described range, the problem of toxicity does not arise at all.
99mTc isoniazid of the invention can be readily prepared by reducing a pertechnetate (99m), e.g., sodium pertechnetate, with a reducing agent in an aqueous solution containing isonicotinoylhydrazine which is widely used as an antituberculosis drug.
An example of the aqueous 99mTc-pertechnetate solution is a sodium 99mTc-technetate solution which can be prepared by a known method, i.e., by milking a commercially available radioactive molybdenum (90Mo)-99mtechnetium generator (Ultra-technekow, Diichi RI Kenkyojo, Tokyo, Japan.) These generators are disclosed, for example, in U.S. Patents 3,833,509, 3,830,746, 3,468,808, 3,382,152, etc. The concentration of 99mac which can be prepared from the 99Mo-99mTc generator by milking is generally about 1 mCi/ml to 100 mCi/ml.
Reducing agents which can be used in the process of the invention include ferrous sulfate, ferrous chloride, stannous chloride, hydrosulfite, sodium borohydride, and sodium thiosulfate.
When the reaction is carried out under acidic conditions, inorganic acids, e.g., sulfuric acid, hydrochloric acid and nitric acid, or organic acids, e.g., ascorbic acid, are used in combination with the above-described reducing agents. It is preferred, among various combinations, to use ferrous sulfate plus sulfuric acid, or stannous chloride plus hydrochloric acid.
On the other hand, when the reaction is effected under alkaline conditions, sodium hydroxide, potassium hydroxide, sodium bicarbonate, or the like is used.
In the process of this invention, isoniazid can be used in an amount of about 10-7 to 10-3 mol, preferably 10-6 to 10-4 mol, per 1 mCi of a pertechnetate. Also the reducing agent can be used in an amount of about 10-7 to 10-4 mol, preferably 10-6 to 10-5 mol, per 1 mCi of a pertechnetate.
The reaction temperature is not critical in the process of the invention. Although the reaction can be carried out, e.g., within the range of from 5 to 100"C, it is convenient and economically advantageous to perform the reaction at room temperature (i.e., 10 to 30"C).
The pH of the reaction solution is most preferably within the range of from 1.0 to 7.0, whereas, under neutral or alkaline conditions, the pH is adjusted within the range of from 7 to 11, preferably from 7 to 9.
The thus-prepared aqueous 99mTc isoniazid solution can be administered to a living body either as such or after being adjusted to about 7.0 in pH by neutralizing with alkalis or acids.
The thus-prepared 99mTc isoniazid solution of the invention can be used as such in the examination. When, however, unreacted 99mTcO4- and free 99etc are present, the 99mTc isoniazid solution may be filtered through a suitable filter and purified by column chromatography using, e.g., an ion exchange resin, to obtain a pure 99mTc isodiazid solution.
The agent to be used in the diagnosis of malignancy in accordance with the invention is, if desired, prepared by the above-described method and is used within the period of from 5 to 60 minutes after the preparation thereof The period within which the agent is to be used is determined by various factors including the half-life (6 hours) of 99mTc and the time required for the 99mac to accumulate on an affected part.
The time required for the 99mTc to accumulate on an affected part varies depending on the manner in which the agent of the invention is administered, the type of disease to be examined, and so forth. In general, it is from 3 to 48 hours, but a type of administration is preferred which permits the accumulation to be achieved within the range of from 8 to 24 hours.
In view of the above-described consideration, it is most preferred for the examination agent of the invention to be administered by intravenous injection. Of course, other administration methods, e.g., oral administration and intraperitoneal administration, can also be employed, and it is to be understood that these methods are also included in the scope of the invention.
When the examination agent of the invention is administered with a syringe, it is most preferable to use physiological saline solution as a dispersant. This makes it possible to prevent the occurrence of injuries to a living body, which are expected to take place when other dispersants are used. Therefore, since the examination agent of the invention is soluble in water, it is believed to be ideal as an in vivo scanning agent.
The invention is hereinafter described in detail with reference to the following examples and animal experiments.
Example 1
4 ml of a 24.4% H2S04 solution was added to 60 mg of FeSO4'7H2O and dissolved by stirring at room temperature for 5 minutes. To the solution thus prepared was added 1 ml (about 10 mCi) of a sodium pertechnetate (Na 99etc04) solution which had been prepared by milking a commercially available 99Mo-99mTc generator (Ultratechnekow, Daiichi RI Kenkyujo), and the mixture was stirred further for 5 minutes. A 1 ml portion of the resulting solution was sampled, to which 80 mg of isoniazid was then added with stirring at room temperature for 10 minutes to obtain a solution. After the reaction was completed, 9N sodium hydroxide was added to the reaction mixture to adjust the pH to 7.0. Then, 1 ml of a phosphate buffer (50 ml of 0.2 M KH2PO4 and 35 ml of 0.2 M NaOH; pH 7.2) was added thereto, and the resulting solution was stirred for 10 minutes. The solution thus prepared was filtered using a membrane filter (diameter: 0.22 um) to obtain a 99mTc isoniazid solution having a labeling ratio of about 80%. Paper chromatographic analysis of the resulting solution showed that the compound prepared above was a pure product containing no impurities such as 99mTcO4-.
Example2
500 mg of isoniazid was dissolved in 40 ml of distilled water, and 4 ml of 1 N hydrochloric acid was added to the resulting solution. To the solution was added 1 ml of a solution prepared by dissolving 200 mg of SnCI2-2H2O in 1 N hydrochloric acid in an amount sufficient to make the total volume exactly 10 ml. Then, 5 ml of a 0.2M aqueous sodium bicarbonate solution was added to the mixture and the total volume of the resulting mixture was adjusted exactly to 100 ml with distilled water.The solution thus prepared was filtered using a membrane filter (diameter: 0.22 yam). To 2 ml of the solution was added 2 ml (about 20 mCi) of a sodium pertechnetate (Na 99mTcO4) solution as used in Example 1, and the mixture was stirred for 1 minute to obtain a 99mTc isoniazid solution having a labeling ratio of about 80%. Paper chromatographic analysis of the resulting solution showed that the compound prepared above was a pure product containing no impurities such as 99mTcO4-.
In order to demonstrate the usefulness of the present compound, the following animal experiments were carried out.
Animal experiment I
Yoshida sarcomatous cells were transplanted subcutaneously in the femoral region of 10 Donryu rats. Six days after the transplantation, 1.3 ml (0.5 mCi) a solution of the 99mac isoniazid composite-containing solution prepared as described in Example 1 (diluted with a physiological saline solution) was injected into each rat bearing intramuscular mastocytoma intravenously through the tail thereof. Eighteen hours after the injection, the rat was anesthetized with urethane, and was sacrificed by drawing blood from the main artery.
The tumor, pectoral muscle, liver, spleen, kidney, lung, stomach, pancreas, os parietale, cerebrum, thymus, heart, thyroid gland, and sexual glands were excised from the rat. For each organ, the weight and radioactivity were measured. The radioactivity accumulation efficiency (% Dose/g) was determined from the ratio of the value of radioactivity measured to the total value of radioactivity administered. The results obtained are shown in the Table 1 below.
TABLE 1
Organ Radioactivity Accumulation
Efficiency (% Dose/g)
Tumor 0.23 + 0.01
Blood 0.12 + 0.00
Pectoral muscle 0.01 + 0.00
Liver 0.28 + 0.02
Spleen 0.35 + 0.03
Kidney 1.68+0.12 Lung 0.23 + 0.04
Stomach 0.06 + 0.00
Pancreas 0.13 + 0.01
Thyroid Gland 0.57 + 0.04
Os Parietale 0.02 + 0.00
Heart 0.12 + 0.00
Cerebrum 0.00 + 0.00
Thymus 0.02 + 0.01
Testis 0.03 + 0.01
An anterior imaging study of one rat treated according to the procedure described in Animal Experiment 1 above taken by a y-camera was shown in Figure.The photograph apparently shows the radioactivity accumulation in Yoshida sarcomatous cells transplanted in the lower left femoral region and the metastatic lesion in the lower central region of the body. The accumulation image at the center of the body is mainly observed in the kidney.
Animal Experiment 2
Ehrlich ascites tumor cells were transplanted subcutaneously in the femoral region of ddY male mice in an amount of lx 106 cells/0.1 ml/mouse. Ten days after transplantation, 0.2 ml (401lCi) of the 99mTc-isoniazid composit-containing solution obtained in Example 1 diluted with a physiological saline solution or 0.2 ml (5 FCi) of 67Ga citrate solution as a control was injected into the mice (each 10 mice) bearing a tuberculum of about 1 cm in diameter intravenously through the tail thereof. Eighteen hours after the injection, the mice were anesthetized with urethane and were sacrificed by drawing blood from the main axillary artery.The tumor, pectoral muscle, liver, spleen, kidney, lung, stomach, pancreas, cranium, cerebrum, thymus, heart, thyroid gland, and sexual glands were excised from the mice. For each organ, the weight and radioactivity were measured. The radioactivity accumulation efficiency (% Dose/g) was determined from the ratio of the value of radioactivity measured to the total value of radioactivity administered. The results obtained are shown in Table 2 below.
TABLE 2
Organ Radioactivity Accumulation
Efficiency (% Dose/g)
99mTc-isoniazid 67Ga-citrate
Tumor 1.57 1 0.15 2.041 0.08
Blood 0.88 1 0.13 1.401 0.08
Pectoral muscle 0.05 + 0.06 0.61 t 0.05
Liver 2.17 + 0.34 4.5510.16 Spleen 0.7510.12 2.23 + 0.17 Kidney 5.42 + 0.75 3.31 + 0.10
Lung 2.08 1 0.32 1.58 0.11
Stomach 0.92 1 0.21 2.63 1 0.28
Pancreas 0.641 0.10 1.241 0.27 Thyroid Gland 0.92 + 0.14 1.78 + 0.13
Os Parietale 0.36 1 0.06 10.02 + 0.58
Heart 1.06 t 0.16 0.83 1 0.08
Cerebrum 0.02 t 0.01 0.09 1 0.01
Thymus 0.40 + 0.05 2.20 + 0.25
Testis 0.56 + 0.08 0.99 1 0.49
Animal Experiment 3
Yoshida sarcomatous cells were transplanted subcutaneously in the femoral region of 10 Donryu rats. Six days after the transplantation, 0.9 ml (0.5 mCi) of a solution of the 99mTe isoniazid composite-containing solution prepared as described in Example 2 (diluted with a physiological saline solution) was injected into each rat bearing intramuscular mastocytoma intravenously through the tail thereof. Eighteen hours after the injection, the rat was anesthetized with urethane and was sacrificed by drawing blood from the main artery.
The tumor, pectoral muscle, liver, spleen, kidney, lung, stomach, pancreas, os parietale, cerebrum, thymus, heart, thyroid gland, and sexual glands were excised from the rat. For each organ, the weight and radioactivity were measured. The radioactivity accumulation efficiency (% Dose/g) was determined from the ratio of the value of radioactivity measured to the total value of radioactivity administered. The results obtained are shown in the Table 3 below.
TABLE 3
Organ Radioactivity Accumulation
Efficiency (% Dose/g)
Tumor 0.31 + 0.01
Blood 0.05 + 0.01
Pectoral muscle 0.01 + 0.00
Liver 0.16 + 0.05
Spleen 0.15 + 0.08
Kidney 1.3510.53 Lung 0.10 + 0.07
Stomach 0.10 + 0.06
Pancreas 0.03 + 0.01
Thyroid Gland 0.08 f 0.02
Os Parietale 0.01 + 0.01
Heart 0.02 + 0.01
Cerebrum 0.00 + 0.00
Thymus 0.01 f 0.01
Testis 0.01 + 0.00
As can be seen from the results shown in Tables 1 to 3 above, with the 99mTc isoniazid of the present invention, the tumor/tissue ratio is high and, furthermore, accumulation on the transferred tumor can be clearly distinguished.Thus, the 99mTc isoniazid of the invention is very useful as a tumor scanning agent.
It is known that the acute toxicity (LD50) of isoniazid as determined by oral, subcutaneous and intravenous administrations in mice is 142 mg/kg, 160 mg/kg and 153 mg, respectively, (Am. Rev. Tuberc. 65,376, 1952).
Also, LD50 as determined in rats is known to be 650 mg/kg by oral administration (Merck Index, 9, 680,76) and 329 mg/kg by subcutaneous administration (Journal of Pharmacology and Experimental Therapeutics, 119,444,57). Thus, the administration of 99mTc-labeled isoniazid in human body at the dose useful as a tumor scanning does not cause any toxicity problem.
While the invention has been described in detail and with reference to specific embodiment thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the scope thereof.
Claims (14)
1. Technetium (99m)-labeled isonicotinoylhydrazine.
2. A process for producing technetium (99m)-labeled isonicotinoylhydrazine which comprises reducing s pertechnetate (99m) with a reducing agent in an isonicotinoylhydrazine containing solution under acidic, alkaline or neutral conditions.
3. The process according to Claim 2, wherein said pertechnetate is sodium pertechnetate.
4. The process as claimed in Claim 2 or 3, wherein the reducing agent is a combination of ferrous sulfate and sulfuric acid.
5. The process as claimed in Claim 2 or 3, wherein the reducing agent is stannous chloride.
6. An agent for use in the diagnosis of malignancy, which contains technetium (99m)-labeled isonicotinoylhydrazine as a major component.
7. A process for reducing technetium (99m)-labeled isonicotinylhydrazine, as claimed in Claim 2 or 3, wherein the reduction is carried out under alkaline conditions utilizing a compound selected from sodium hydroxide, potassium hydroxide and sodium bicarbonate.
8. A process for producing technetium (99m)-labeled isonicotinyl hydrazine, as claimed in Claim 7, wherein the reduction is carried out at a temperature from about 5 to 100 C.
9. A proceess for producing technetium (99m)-labeled isonicotinylhydrazine, as claimed in Claim 8, wherein the reduction is carried out at a temperature between 1 0C to 30"C.
10. A process for producing technetium (99m)-labeled isonicotinylhydrazine, as claimed in Claim 2,3,4 or 5 wherein the reaction solution has a pH of from 1.0 to 7.0.
11. A process for producing technetium (99m)-labeled isonicotinylhydrazine, as claimed in Claim 7,8 or 9, wherein the pH is adjusted to within the range of from 7.0 to 11.0.
12. A process for producing technetium (99m)-labeled isonicotinylhydrazine, as claimed in Claim 11, wherein the pH is adjusted within the range of from 7.0 to 9.0.
13. A process as claimed in Claim 2, substantially as hereinbefore described in Examples 1 or 2.
14. Technetium (99m) labeled isonicotinylhydrazine when produced by a process as claimed in any one of Claims 2 to 13.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56065981A JPS57181058A (en) | 1981-04-30 | 1981-04-30 | Compound labeled with 99m technetium, and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2101118A true GB2101118A (en) | 1983-01-12 |
Family
ID=13302684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08212520A Withdrawn GB2101118A (en) | 1981-04-30 | 1982-04-29 | Technetium (99m)-labeled compound and process for production of said compound |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS57181058A (en) |
| DE (1) | DE3216026A1 (en) |
| FR (1) | FR2504926A1 (en) |
| GB (1) | GB2101118A (en) |
| NL (1) | NL8201788A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1985003063A1 (en) * | 1983-12-29 | 1985-07-18 | The Commonwealth Of Australia | PREPARATION OF 99mTC RADIOPHARMACEUTICALS |
| US5206370A (en) * | 1989-02-24 | 1993-04-27 | Johnson Matthey, Inc. | Certain pyridyl hydrazines and hydrazides useful for protein labeling |
| WO1993010822A1 (en) * | 1991-12-05 | 1993-06-10 | The Du Pont Merck Pharmaceutical Company | TECHNETIUM-99 m COMPLEXES WITH N-SUBSTITUTED 3-HYDROXY-4-PYRIDINONES |
| US6124440A (en) * | 1989-08-29 | 2000-09-26 | Nycomed Amersham Plc | Cores for technetium radiopharmaceuticals |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL93432A (en) * | 1989-02-24 | 1994-02-27 | Johnson Mathey Inc | Hydrazines and hydrazides, their conjugates with macromolecules and such conjugates labelled with metal ions |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2794019A (en) * | 1952-12-10 | 1957-05-28 | Schenley Ind Inc | Metal complexes of isoniazid |
| US4193979A (en) * | 1978-05-22 | 1980-03-18 | G. D. Searle & Co. | Sodium 3-[[[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]-amino]carbonyl]-2-pyridinecarboxylic acid and related compounds labeled with technetium-99m |
-
1981
- 1981-04-30 JP JP56065981A patent/JPS57181058A/en active Pending
-
1982
- 1982-04-29 GB GB08212520A patent/GB2101118A/en not_active Withdrawn
- 1982-04-29 DE DE19823216026 patent/DE3216026A1/en not_active Withdrawn
- 1982-04-29 NL NL8201788A patent/NL8201788A/en not_active Application Discontinuation
- 1982-04-30 FR FR8207591A patent/FR2504926A1/en not_active Withdrawn
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1985003063A1 (en) * | 1983-12-29 | 1985-07-18 | The Commonwealth Of Australia | PREPARATION OF 99mTC RADIOPHARMACEUTICALS |
| US4851515A (en) * | 1983-12-29 | 1989-07-25 | The Commonwealth Of Australia | Preparation of 99m Tc radiopharmaceuticals |
| US4923969A (en) * | 1983-12-29 | 1990-05-08 | The Commonwealth Of Australia | Preparation of 99m Tc radiopharmaceuticals |
| US5206370A (en) * | 1989-02-24 | 1993-04-27 | Johnson Matthey, Inc. | Certain pyridyl hydrazines and hydrazides useful for protein labeling |
| US5420285A (en) * | 1989-02-24 | 1995-05-30 | Johnson Matthey, Inc. | Protein labelling utilizing certain pyridyl hydrazines, hydrazides and derivatives |
| US5753520A (en) * | 1989-02-24 | 1998-05-19 | Johnson Matthey Inc. | Protein labelling |
| US6217845B1 (en) | 1989-02-24 | 2001-04-17 | Anormed, Inc. | Protein labelling |
| US6124440A (en) * | 1989-08-29 | 2000-09-26 | Nycomed Amersham Plc | Cores for technetium radiopharmaceuticals |
| US6329513B1 (en) | 1989-08-29 | 2001-12-11 | Nycomed Amersham Plc | Cores for technetium radiopharmaceuticals |
| US6515112B2 (en) | 1989-08-29 | 2003-02-04 | Amersham Plc | Cores for technetium radiopharmaceuticals |
| WO1993010822A1 (en) * | 1991-12-05 | 1993-06-10 | The Du Pont Merck Pharmaceutical Company | TECHNETIUM-99 m COMPLEXES WITH N-SUBSTITUTED 3-HYDROXY-4-PYRIDINONES |
| US5336482A (en) * | 1991-12-05 | 1994-08-09 | The Du Pont Merck Pharmaceutical Company | Technetium-99m complexes with N-substituted 3-hydroxy-4-pyridinones |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57181058A (en) | 1982-11-08 |
| NL8201788A (en) | 1982-11-16 |
| FR2504926A1 (en) | 1982-11-05 |
| DE3216026A1 (en) | 1982-11-11 |
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