Classifications

• • G—PHYSICS
  • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
  • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
  • G21G4/00—Radioactive sources
  • G21G4/04—Radioactive sources other than neutron sources
  • G21G4/06—Radioactive sources other than neutron sources characterised by constructional features
  • G21G4/08—Radioactive sources other than neutron sources characterised by constructional features specially adapted for medical application
• • 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
  • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G99/00—Subject matter not provided for in other groups of this subclass
  • C01G99/006—Compounds containing, besides a metal not provided for elsewhere in this subclass, two or more other elements other than oxygen or hydrogen
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2121/00—Preparations for use in therapy

Definitions

• Radiopharmaceutical consists of a radioactive portion which emits radioactivity that can be detected by a suitable detector, and a ligand portion which is non-radioactive and which allows the compound to enter into chemical reactions within the patient's body.
• the ligand portion is selected from a range of suitable ligands, the choice being dependent upon the presumed diagnosis of the disease being investigated since it is the chemical properties of the ligand which determine the chemical reactions the radiopharmaceutical will participate in, and hence where in the body it will be distributed.
• the emitted radiation may be detected by the detector in order to follow the metabolic or other distribution pathways of the administered radioactive chemical.
• the distribution of the radioactive chemical within the patient's body and throughout the various organs by pathological and physiological processes may be monitored and studied.
• Technetium ( 99m Tc) is usually obtained from a molybdenum 99 generator in the form of a saline solution of pertechnetate ion, TcO 4 - , in which the technetium is in the +7 oxidation state.
• Technetium in this form is not suitable for reaction with the various ligands usually used to form radiopharmaceuticals, and in general it must be reduced to the technetium cation in either the +3 or +4 oxidation state prior to the reaction with the selected ligand.
• the reduction of technetium is usually achieved by reacting the pertechnetate ion with a stannous chloride (SnCl 2 ) solution. It has been found, however, that the stannous chloride solution must be freshly prepared since it readily undergoes atmospheric oxidation, particularly in the presence of saline.
• kits which involve the direct reaction between the stannous ions, the technetium in the form of the pertechnetate ion, and the selected ligand, with the stannous ions being in excess to ensure that all of the pertechnetate ion is converted to a lower oxidation state.
• a typical commercially available kit comprises a sealed, sterile container containing a powdered mixture of stannous chloride and the selected ligand. Immediately prior to use, the seal on a sterile container is broken and a saline solution of pertechnetate ion is added to the container.
• stannous chloride injected into the patient as discussed above can enter into unwanted metabolic reactions and alterations during and after the studies on the patient such as, for example, following a bone scan using technetium-labelled methylendiphosphonate. Furthermore, stannous chloride present in the general body circulation makes it difficult to perform some other scan studies on the same patient within a reasonably short time.
• a method of reducing a radioactive material particularly reducing pertechnetate ion to Tc(III) or Tc(IV) which method comprises the steps of depositing a suitable reducing agent onto a surface, for example the internal wall of a reaction vessel, and reacting the radioactive material with the reducing agent by contacting a solution containing the radioactive material with the surface thereby reducing the radioactive material and providing a solution containing reduced radioactive material substantially free of reducing agent.
• a silicon-containing material such as dimethyl-siloxane may be applied to the internal surface of the reaction vessel before deposition of the reducing agent, however this is not essential.
• kits for producing a radioactive labelled ligand suitable for use as an injectable radiopharmaceutical comprising a reaction vessel having a reducing agent deposited on an inner surface thereof, means for admitting a radioactive material to the reaction vessel and means for admitting a ligand to be labelled by the radioactive material to the reaction vessel, whereby the radioactive material is reduced and ligand is labelled by the reduced radioactive material within the reaction vessel, and means for discharging the radioactive-labelled ligand substantially free of the reducing agent from the reaction vessel.
• ligands include, for instance, plasma proteins such as human serum albumin (HSA), ethylhydroxydiphosphonate (EHDP), methylenediphosphonate (MDP), pyrophosphate, ethylenediamin ⁇ tetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), dimercaptosuccinic acid (DSMA), gluconate, glucoheptonate, N-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (HIDA), analogs of HIDA such as N-(2,6-diisopropylphenylcarbamoylmethyl) iminodiacetic acid (PRIDA), N-(4-butylphenylcarbamoylmethyl)- iminodiacetic acid (BIDA), clotting factors such as fibrinogen, gamma globulins, antibodies and their fractions, phytate, and the like.
• HSA human serum albumin
• FIGURE 3 is a kidney scan of rabbit using 9 9m Tc-labelled diethylenetriamine penta-acetic acid (DTPA) prepared in accordance with the present invention shown in three different intensities.
• DTPA diethylenetriamine penta-acetic acid
• any suitable material such as glass or plastic may form a suitable reaction vessel.
• a sterile non-pyrogenic polyethylene catheter pipette was used, the internal surface of the pipette was washed with dimethyl-siloxane in order to make the internal bore of the catheter smooth by depositing silicon on it.
• a polyethylene syringe may be used as the reaction vessel in place of the catheter pipette.
• a solution of Sigmacote which is a commercially available silicone solution from Sigma Inc. may be used.
• siliconizing the surface of the reaction vessel is an optional step, although siliconised vessels have been found to assist in some instances in prevention of microcolloid formation.
• the pertechnetate ion is reduced and the ligand complex is formed i.e. the ligand is labelled by the technetium.
• Watman No. 1 which are cut into strips typically about 7 mm wide by 57 mm long. These strips which are used with the saline medium are marked transversely with a graphite pencil about 10 mm from one end. Similarly, the strips which are used with the methyl ethyl ketone are marked about 10 mm from the same one end.
• strip A is inserted vertically into a flat-bottomed vial containing saline solution to a depth of about 2 to 3 mm and strip B is inserted into a flat bottom vial containing methyl ethyl ketone to a depth of about 2 to 3 mm.
• strip B is inserted into a flat bottom vial containing methyl ethyl ketone to a depth of about 2 to 3 mm.
• the strips are removed from the vial. They are then cut at the pencil marks and the two components are placed in counting tubes for measurement in a well counter or a dose calibrator. These sections are designated as A 1 and A 2 for strip A and B 1 and B 2 for strip B.
• One of the advantages of the present invention is that there is none or at worst a negligible amount (about ⁇ 4 ⁇ g) of stannous chloride injected into the biological system of the patient receiving the invention. Accordingly, there is less chance of there being adverse side reactions in the patient and interference with subsequent treatments and investigations.

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Physics & Mathematics (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• Optics & Photonics (AREA)
• Pharmacology & Pharmacy (AREA)
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• Inorganic Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Dispersion Chemistry (AREA)
• Veterinary Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• General Engineering & Computer Science (AREA)
• High Energy & Nuclear Physics (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

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Citations (5)

• 1984
  • 1984-12-06 EP EP19850900015 patent/EP0163701A1/de not_active Withdrawn
  • 1984-12-06 WO PCT/AU1984/000253 patent/WO1985002604A1/en unknown

Patent Citations (5)

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