Classifications

• • 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)
• Electromechanical Clocks (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Priority Applications (8)

Applications Claiming Priority (1)

Publications (1)

Family

ID=23611956

Family Applications (1)

Country Status (8)

Cited By (11)

Citations (3)

• 1973
  • 1973-10-18 US US407409A patent/US3928552A/en not_active Expired - Lifetime
• 1974
  • 1974-09-25 GB GB4171674A patent/GB1441506A/en not_active Expired
  • 1974-10-02 DE DE19742447556 patent/DE2447556A1/de not_active Withdrawn
  • 1974-10-14 NL NL7413506A patent/NL7413506A/xx not_active Application Discontinuation
  • 1974-10-16 FR FR7434814A patent/FR2248055B1/fr not_active Expired
  • 1974-10-17 JP JP49119877A patent/JPS585887B2/ja not_active Expired
  • 1974-10-17 CH CH1393274A patent/CH609564A5/fr not_active IP Right Cessation
  • 1974-10-17 IT IT53586/74A patent/IT1050251B/it active

Patent Citations (3)

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