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US3928552A - Hepato-biliary radiopharmaceutical comprising 2-mercaptoisobutyric acid chelating reduced technetium-99m - Google Patents

Hepato-biliary radiopharmaceutical comprising 2-mercaptoisobutyric acid chelating reduced technetium-99m Download PDF

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US3928552A
US3928552A US407409A US40740973A US3928552A US 3928552 A US3928552 A US 3928552A US 407409 A US407409 A US 407409A US 40740973 A US40740973 A US 40740973A US 3928552 A US3928552 A US 3928552A
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radiopharmaceutical
technetium
mercaptoisobutyric acid
liver
imaging
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US407409A
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Harry S Winchell
Archie S Khentigan
Hong Lin
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US Department of Energy
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Medi Physics Inc
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Priority to US407409A priority Critical patent/US3928552A/en
Priority to GB4171674A priority patent/GB1441506A/en
Priority to DE19742447556 priority patent/DE2447556A1/en
Priority to NL7413506A priority patent/NL7413506A/en
Priority to FR7434814A priority patent/FR2248055B1/fr
Priority to IT53586/74A priority patent/IT1050251B/en
Priority to JP49119877A priority patent/JPS585887B2/en
Priority to CH1393274A priority patent/CH609564A5/fr
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Assigned to UNITED STATES OF AMERICA, AS REPRESENTED BY THE UNITED STATES DEPARTMENT OF ENERGY reassignment UNITED STATES OF AMERICA, AS REPRESENTED BY THE UNITED STATES DEPARTMENT OF ENERGY ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: MEDI-PHYSICS, INC.
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Definitions

  • ABSTRACT A radiophannaeeutical comprising 2- mercaptoisobutyric acid chelating reduced technetium-99m for scintigraphically imaging the liver and biliary tract morphology and function and to a method for instantly making the radiopharmaceutical.
  • This invention relates generally to such hepato-biliary imaging radiopharmaceuticals and more particularly to a new liver specific radiopharmaceutical useful for studying liver, gall bladder and biliary tract morphology and function.
  • the pharmaceutical consists of an aqueous solution of 2-mercaptoisobutyric acid chelating reduced 99mtechnetium.
  • a preferred form utilizes stannous tin as a reducing agent for the technetium-99m.
  • the imaging agent is simply and rapidly prepared by mixing a reagent containing the Z-mercaptoisobutyric acid and stannous tin with oxidant-free technetium- 99m pertechnetate which is readily available in physiological saline solution.
  • the principal object of this invention is to produce a technetium-99m radiopharmaceutical which rapidly accumulates in the liver and then is excreted from the liver to the biliary tract so as to be useful for hepaticbiliary morphology and function studies.
  • Another object of this invention is to produce such a radiopharmaceutical in a simple and rapid labeling procedure which does not involve heating or complicated pH adjustment.
  • the radiopharmaceutical has been prepared from a reagent made by mixing qual parts by volume of an aqueous solution of 3mM 2-mercaptoisobutyric acid and 1mm stannous chloride. To one part by volume of reagent is added one part of oxidant-free 99m-technetium pertechnetate in physiological saline solution. The combined solutions are mixed thoroughly by shaking. The technetium labeling is rapid. The binding of 99m-technetium is essentially complete immediately after mixing and the agent is immediately ready for intravenous administration. The radiopharmaceutical should be used within two hours after preparation.
  • the pH of 3 mM Lmercaptoisobutyric acid is about 2.9 and the pH range of the reagent of the specific example above is 2.5 to 3.5. Varying concentrations of stannous chloride or varying proportions of reagent to technetium-99m pertechnetate also do not significantly affect in vivo distribution.
  • the activity distributes inthe blood plasma from which it is cleared by the liver exponentially, with a half-time of less than two minutes.
  • the initial clearance rate is comparable to that obtained with intravenously administered radiocolloids in the same animal species and extraction efficiency of the liver is almost 100%.
  • the slope of the disappearance curve for radioactivity in the blood plasma diminishes after five minutes, becoming fairly flat at 30 minutes with approximately five percent of the administered dose remaining in the blood plasma at that time. There is negligible uptake in the kidneys and spleen.
  • the radiopharmaceutical is particularly useful for liver-biliary tract function studies.
  • scintiphotographs taken of experimental dogs following intravenous ad ministration using a standard pinhole collimator fitted to a Nuclear Chicago H-P scintillation camera the liver was clearly visualized seven minutes after administration comparable to that obtained using 99m-technetium labeled colloids, except that there was no activity seen in the spleen.
  • the gall bladder was visualized and at 60 minutes after administration the gall bladder activity was predominant.
  • Scintiphotographs taken to 120 minutes after administration showed with good resolution the activity in the common bile duct and in the region of the ampula.
  • Reducing agents for technetium-99m other than stannous tin may be used to make the described pharmaceutical, i.e., ferrous, titanous, zirconyl and chromous ions as well as Z-mercaptoisobutyric acid itself in high concentration or low pH or elevated temperature as is known in the art.
  • An hepato-biliary scintographic agent has been formed by (a) heating technetium-99m pertechnetate in the presence of 2-mercaptoisobutyric acid (MIBA) for 15 minutes at 100C or (b) by contacting technetium-99m pertechnetate with high concentrations of Z-mercaptoisobutyric acid (MlBA), e.g. greater than millimolar, for several hours.
  • MIBA 2-mercaptoisobutyric acid
  • MlBA Z-mercaptoisobutyric acid
  • a radiopharmaceutical for scintigraphic organ imaging comprising Z-mercaptoisobutyric acid labeled with reduced technetium-99m.
  • a radiopharmaceutical consisting of mixed aqueous solutions of Z-mercaptoisobutyric acid and stannous chloride; and technetium-99m pertechnetate in physiological saline.
  • the method of making an instantly labeled liver specific radiopharmaceutical comprising the steps of preparing a reagent of mixed aqueous solutions of 2-n1ercaptoisobutyric acid and stannous chloride;
  • the method of serially imaging the liver and biliary tract of a patient comprising the steps of preparing a radiopharmaceutical from Z-mercaptoisobutyric acid and technetium-99m maintained in the reduced state by the presence of stannous tin;
  • the method of imaging localized pathologic lesions in a patient comprising the steps of preparing a radiopharmaceutical from 2-mercaptoisobutyric acid labeled with reduced technetium- 99m;

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A radiopharmaceutical comprising 2-mercaptoisobutyric acid chelating reduced technetium-99m for scintigraphically imaging the liver and biliary tract morphology and function and to a method for instantly making the radiopharmaceutical.

Description

United States Patent Winchell et al.
[ Dec. 23, 1975 HEPATO-BILIARY RADIOPHARMACEUTICAL COMPRISING Z-MERCAPTOISOBUTYRIC ACID CHELATING REDUCED TECHNETIUM-99M Inventors: Harry S. Winchell, Lafayette;
Archie S. Khentigan, San Francisco; Hong Lin, Berkeley, all of Calif.
Assignee: Medi-Physics, Inc Emeryville,
Calif.
Filed: Oct. 18, 1973 Appl. No.: 407,409
US. Cl 424/ 1; 250/303; 260/429 R; 260/429.7
Int. Cl. A6lk 27/04; C07f 7/22; GOlt 1/00 Field of Search 424/ 1; 260/429.7, 429 J, 260/429 K, 429 R; 250/303, 363
[56] References Cited UNIT ED STATES PATENTS 3,725,295 4/1973 Eckelman et al. 252/301.1 R 3,749,913 7/1973 Halpern et al 424/1 X 3,824,399 7/1974 Bjork et al. 250/303 X Primary Examiner-Benjamin R. Padgett Assistant Examiner-C. Nucker Attorney, Agent, of FirmSamuel L. Welt; Jon S. Saxe; R. Hain Swope [57] ABSTRACT A radiophannaeeutical comprising 2- mercaptoisobutyric acid chelating reduced technetium-99m for scintigraphically imaging the liver and biliary tract morphology and function and to a method for instantly making the radiopharmaceutical.
7 Claims, N0 Drawings HEPATolL ARy RADIOPIIARIl/IACEUTICAL COMPRISING Z-MERACAPTOISOBUTIYRIC, ACID CHELATING REDUCED TECHNETIUM-99M BACKGROUND OF THE INVENTION Heretofore, various dyes have been labeled with iodine radioisotopes for combined imaging of the liver and biliary tract. An imaging agentsuch as iodine-131 labeled rose bengal' has proven useful; however, the relatively high radiation dose associated with it has limited the extent of its use. The Journal of Nuclear Medicine, August, 1972, Vol. 13 No. 8, atpages 652-4, suggests use of technetium-99m labeled D-penicillamine as a cholescintigraphic agent prepared *in acid solution, heatedand then neutralized before use. The Journal ofNucIear Medicinegtlune I973, Vol. 14 No. 6 at pages 41 1-12, suggests several technetium-mercaptide derivatives as liverspecific imaging agents; These technetium labeled agents would result in diminished absorbed radiation doses.
SPECIFICATION This invention relates generally to such hepato-biliary imaging radiopharmaceuticals and more particularly to a new liver specific radiopharmaceutical useful for studying liver, gall bladder and biliary tract morphology and function.
The pharmaceutical consists of an aqueous solution of 2-mercaptoisobutyric acid chelating reduced 99mtechnetium. A preferred form utilizes stannous tin as a reducing agent for the technetium-99m. In this form the imaging agent is simply and rapidly prepared by mixing a reagent containing the Z-mercaptoisobutyric acid and stannous tin with oxidant-free technetium- 99m pertechnetate which is readily available in physiological saline solution.
In vivo distribution studies of the labeled material in experimental animals after intravenous injection show initial rapid clearance of the radioactivity from the blood plasma specifically by the liver with subsequent, almost complete, excretion into the biliary tract.
The principal object of this invention is to produce a technetium-99m radiopharmaceutical which rapidly accumulates in the liver and then is excreted from the liver to the biliary tract so as to be useful for hepaticbiliary morphology and function studies.
Another object of this invention is to produce such a radiopharmaceutical in a simple and rapid labeling procedure which does not involve heating or complicated pH adjustment.
Other objects and advantages of the new pharmaceutical and method will become apparent upon consideration of the following description of a specific example.
The radiopharmaceutical has been prepared from a reagent made by mixing qual parts by volume of an aqueous solution of 3mM 2-mercaptoisobutyric acid and 1mm stannous chloride. To one part by volume of reagent is added one part of oxidant-free 99m-technetium pertechnetate in physiological saline solution. The combined solutions are mixed thoroughly by shaking. The technetium labeling is rapid. The binding of 99m-technetium is essentially complete immediately after mixing and the agent is immediately ready for intravenous administration. The radiopharmaceutical should be used within two hours after preparation.
Other proportions of Z-mercaptoisobutyric acid and stannous chloride canbe used. No significant difference in in vivo distribution has been noted if the labeled pha rmaceutical i'sprepared from reagent made with 1 mM stannous chloride mixed with an equal volume of 3, 5, 7.5 orl mK/l concentrations of 2-mercaptoisobutyric acid. Similarly, no significant difference in the in vivo distribution was observed for the radiopharmaceutical wherein the reagent was prepared with equzivolumes of 1 mm stannous chloride and various 3 mM solutions of 2-mercaptoisobutyric acid adjuste d in pH through the range of 2.9 to 7. The pH of 3 mM Lmercaptoisobutyric acid is about 2.9 and the pH range of the reagent of the specific example above is 2.5 to 3.5. Varying concentrations of stannous chloride or varying proportions of reagent to technetium-99m pertechnetate also do not significantly affect in vivo distribution.
Following intravenous administration of the pharmaceutical in experimental animals, the activity distributes inthe blood plasma from which it is cleared by the liver exponentially, with a half-time of less than two minutes. The initial clearance rate is comparable to that obtained with intravenously administered radiocolloids in the same animal species and extraction efficiency of the liver is almost 100%. The slope of the disappearance curve for radioactivity in the blood plasma diminishes after five minutes, becoming fairly flat at 30 minutes with approximately five percent of the administered dose remaining in the blood plasma at that time. There is negligible uptake in the kidneys and spleen.
For example, in experimental rats, as early as five minutes after administration over of the remaining activity was in the liver and 6% in the gut. The liver activity progressively cleared through the biliary tract to the gut. Three hours after administration, approximately 4% of the remaining activity was in the liver and 91% was found in the gut. Activity in the kidneys and spleen of animals sacrificed one hour after administration was negligible. Approximately 93% of the administered activity was found to have been excreted from the body within 24 hours after its administration.
The radiopharmaceutical is particularly useful for liver-biliary tract function studies. In scintiphotographs taken of experimental dogs following intravenous ad ministration using a standard pinhole collimator fitted to a Nuclear Chicago H-P scintillation camera, the liver was clearly visualized seven minutes after administration comparable to that obtained using 99m-technetium labeled colloids, except that there was no activity seen in the spleen. At thirty minutes, the gall bladder was visualized and at 60 minutes after administration the gall bladder activity was predominant. Scintiphotographs taken to 120 minutes after administration showed with good resolution the activity in the common bile duct and in the region of the ampula.
The foregoing example and distribution data are illustrative of the improved pharmaceutical and the simple method for instantly making it. Reducing agents for technetium-99m other than stannous tin may be used to make the described pharmaceutical, i.e., ferrous, titanous, zirconyl and chromous ions as well as Z-mercaptoisobutyric acid itself in high concentration or low pH or elevated temperature as is known in the art. An hepato-biliary scintographic agent has been formed by (a) heating technetium-99m pertechnetate in the presence of 2-mercaptoisobutyric acid (MIBA) for 15 minutes at 100C or (b) by contacting technetium-99m pertechnetate with high concentrations of Z-mercaptoisobutyric acid (MlBA), e.g. greater than millimolar, for several hours.
In view of the fact that various radiopharmaceuticals which do not accumulate generally in normal tissue other than the target organ being studied, have been found to localize in infarcts and tumors, the described radiopharmaceutical may have utility in radioisotope study of localized pathologic lesions. The scope of the invention is defined in the appended claims.
We claim:
1. A radiopharmaceutical for scintigraphic organ imaging comprising Z-mercaptoisobutyric acid labeled with reduced technetium-99m.
2. The radiopharmaceutical of claim 1 wherein the 2-mercaptoisobutyric acid is in aqueous solution and the technetium-99m is maintained in the reduced state by the presence of stannous tin.
3. A radiopharmaceutical consisting of mixed aqueous solutions of Z-mercaptoisobutyric acid and stannous chloride; and technetium-99m pertechnetate in physiological saline.
4. The radiopharmaceutical of claim 3 wherein the molar proportion of the Z-mercaptoisobutyric acid to stannous chloride is 3 to l.
5. The method of making an instantly labeled liver specific radiopharmaceutical comprising the steps of preparing a reagent of mixed aqueous solutions of 2-n1ercaptoisobutyric acid and stannous chloride;
and
then adding to said reagent technetium-99m pertechnetate ions in physiological saline solution.
6. The method of serially imaging the liver and biliary tract of a patient comprising the steps of preparing a radiopharmaceutical from Z-mercaptoisobutyric acid and technetium-99m maintained in the reduced state by the presence of stannous tin;
intravenously injecting the patient with said radiopharmaceutical; and then scintigraphically imaging the liver and biliary tract to follow movement of radioactivity into the liver and then from it through the biliary tract.
7. The method of imaging localized pathologic lesions in a patient comprising the steps of preparing a radiopharmaceutical from 2-mercaptoisobutyric acid labeled with reduced technetium- 99m;
intravenously injecting the patient with said radiopharmaceutical; and
then scintigraphically imaging the lesion.

Claims (7)

1. A RADIOPHARMACEUTICAL FOR SCINTIGRAPHIC ORGAN IMAGING COMPRISING 2-MERCAPTOISOBUTYRIC ACID LABELED WITH REDUCED TECHNETIUM-99M.
2. The radiopharmaceutical of claim 1 wherein the 2-mercaptoisobutyric acid is in aqueous solution and the technetium-99m is maintained in the reduced state by the presence of stannous tin.
3. A radiopharmaceutical consisting of mixed aqueous solutions of 2-mercaptoisobutyric acid and stannous chloride; and technetium-99m pertechnetate in physiological saline.
4. The radiopharmaceutical of claim 3 wherein the molar proportion of the 2-mercaptoisobutyric acid to stannous chloride is 3 to 1.
5. The method of making an instantly labeled liver specific radiopharmaceutical comprising the steps of preparing a reagent of mixed aqueous solutions of 2-mercaptoisobutyric acid and stannous chloride; and then adding to said reagent technetium-99m pertechnetate ions in physiological saline solution.
6. The method of serially imaging the liver and biliary tract of a patient comprising the steps of preparing a radiopharmaceutical from 2-mercaptoisobutyric acid and technetium-99m maintained in the reduced state by the presence of stannous tin; intravenously injecting the patient with said radiopharmaceutical; and then scintigraphically imaging the liver and biliary tract to follow movement of radioactivity into the liver and then from it through the biliary tract.
7. The method of imaging localized pathologic lesions in a patient comprising the steps of preparing a radiopharmaceutical from 2-mercaptoisobutyric acid labeled with reduced technetium-99m; intravenously injecting the patient with said radiopharmaceutical; and then scintigraphically imaging the lesion.
US407409A 1973-10-18 1973-10-18 Hepato-biliary radiopharmaceutical comprising 2-mercaptoisobutyric acid chelating reduced technetium-99m Expired - Lifetime US3928552A (en)

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Application Number Priority Date Filing Date Title
US407409A US3928552A (en) 1973-10-18 1973-10-18 Hepato-biliary radiopharmaceutical comprising 2-mercaptoisobutyric acid chelating reduced technetium-99m
GB4171674A GB1441506A (en) 1973-10-18 1974-09-25 Chelated technetium-99m
DE19742447556 DE2447556A1 (en) 1973-10-18 1974-10-02 RADIOPHARMACEUTICAL
NL7413506A NL7413506A (en) 1973-10-18 1974-10-14 PROCESS FOR PREPARING A RADIOLOGICAL PHARMACEUTICAL AGENT.
FR7434814A FR2248055B1 (en) 1973-10-18 1974-10-16
IT53586/74A IT1050251B (en) 1973-10-18 1974-10-17 PROCESS TO MAKE A RADIOACTIVE TRACKING COMPOUND AND ITS PRODUCT
JP49119877A JPS585887B2 (en) 1973-10-18 1974-10-17 Housiyaseiiyakuhin Oyobisono Seizouhouhou
CH1393274A CH609564A5 (en) 1973-10-18 1974-10-17

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CH (1) CH609564A5 (en)
DE (1) DE2447556A1 (en)
FR (1) FR2248055B1 (en)
GB (1) GB1441506A (en)
IT (1) IT1050251B (en)
NL (1) NL7413506A (en)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4091088A (en) * 1975-02-19 1978-05-23 Australian Atomic Energy Commission Phenolic amino-carboxylic acid complexes for forming radiopharmaceuticals
US4208398A (en) * 1973-04-23 1980-06-17 Hoffman-La Roche Inc. Technetium-labeled complexes, production and use thereof
US4233285A (en) * 1973-05-14 1980-11-11 Medi-Physics, Inc. Mercaptocarboxylic acid radiopharmaceuticals
US4298591A (en) * 1979-04-03 1981-11-03 The United States Of America As Represented By The United States Department Of Energy Instantaneous radioiodination of rose bengal at room temperature and a cold kit therefor
US4387087A (en) * 1980-04-18 1983-06-07 Research Corporation Cationic lipophilic complexes of 99m Tc and their use for myocardial and hepatobiliary imaging
US4489054A (en) * 1980-04-18 1984-12-18 Research Corporation Cationic lipophilic complexes of 99m Tc and their use for myocardial and hepatobiliary imaging
US4670545A (en) * 1984-05-11 1987-06-02 University Patents, Inc. Chelating agents for technetium-99M
US4673562A (en) * 1983-08-19 1987-06-16 The Children's Medical Center Corporation Bisamide bisthiol compounds useful for making technetium radiodiagnostic renal agents
US5116596A (en) * 1986-12-10 1992-05-26 Hoechst Aktiengesellschaft Process for the preparation of an organ-specific substance labeled with technetium-99m
US20030194365A1 (en) * 2002-04-15 2003-10-16 Park Kyung Bae Method for labelling technetium or rhenium using borohydride exchange resin
US8942067B2 (en) 2012-03-23 2015-01-27 Omega S.A. Mechanism for displaying and correcting the state of two different time measurable quantities

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3725295A (en) * 1971-07-20 1973-04-03 Atomic Energy Commission Technetium labeling
US3749913A (en) * 1971-06-24 1973-07-31 Administrator Of The Veterans Renal scanning composition and method using technetium 99m
US3824399A (en) * 1971-01-27 1974-07-16 Saab Scania Ab Method of in vivo examination of organ functions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3824399A (en) * 1971-01-27 1974-07-16 Saab Scania Ab Method of in vivo examination of organ functions
US3749913A (en) * 1971-06-24 1973-07-31 Administrator Of The Veterans Renal scanning composition and method using technetium 99m
US3725295A (en) * 1971-07-20 1973-04-03 Atomic Energy Commission Technetium labeling

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4208398A (en) * 1973-04-23 1980-06-17 Hoffman-La Roche Inc. Technetium-labeled complexes, production and use thereof
US4233285A (en) * 1973-05-14 1980-11-11 Medi-Physics, Inc. Mercaptocarboxylic acid radiopharmaceuticals
US4091088A (en) * 1975-02-19 1978-05-23 Australian Atomic Energy Commission Phenolic amino-carboxylic acid complexes for forming radiopharmaceuticals
US4298591A (en) * 1979-04-03 1981-11-03 The United States Of America As Represented By The United States Department Of Energy Instantaneous radioiodination of rose bengal at room temperature and a cold kit therefor
US4387087A (en) * 1980-04-18 1983-06-07 Research Corporation Cationic lipophilic complexes of 99m Tc and their use for myocardial and hepatobiliary imaging
US4489054A (en) * 1980-04-18 1984-12-18 Research Corporation Cationic lipophilic complexes of 99m Tc and their use for myocardial and hepatobiliary imaging
US4673562A (en) * 1983-08-19 1987-06-16 The Children's Medical Center Corporation Bisamide bisthiol compounds useful for making technetium radiodiagnostic renal agents
US4670545A (en) * 1984-05-11 1987-06-02 University Patents, Inc. Chelating agents for technetium-99M
US5116596A (en) * 1986-12-10 1992-05-26 Hoechst Aktiengesellschaft Process for the preparation of an organ-specific substance labeled with technetium-99m
US20030194365A1 (en) * 2002-04-15 2003-10-16 Park Kyung Bae Method for labelling technetium or rhenium using borohydride exchange resin
US6979431B2 (en) * 2002-04-15 2005-12-27 Korea Atomic Energy Research Institute Method for labelling technetium or rhenium using borohydride exchange resin
US8942067B2 (en) 2012-03-23 2015-01-27 Omega S.A. Mechanism for displaying and correcting the state of two different time measurable quantities

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FR2248055A1 (en) 1975-05-16
FR2248055B1 (en) 1978-07-21
JPS50111222A (en) 1975-09-01
NL7413506A (en) 1975-04-22
CH609564A5 (en) 1979-03-15
GB1441506A (en) 1976-07-07
JPS585887B2 (en) 1983-02-02
DE2447556A1 (en) 1975-04-30
IT1050251B (en) 1981-03-10

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