US3812264A - Method of producing a carrier for a scintigraphic preparation and scintigraphic preparations including said carrier - Google Patents

Method of producing a carrier for a scintigraphic preparation and scintigraphic preparations including said carrier Download PDF

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Publication number
US3812264A
US3812264A US00033989A US3398970A US3812264A US 3812264 A US3812264 A US 3812264A US 00033989 A US00033989 A US 00033989A US 3398970 A US3398970 A US 3398970A US 3812264 A US3812264 A US 3812264A
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scintigraphic
carrier
preparation
producing
stannous chloride
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US00033989A
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J Nouel
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MAALLINCKRODT DIAGNOSTICA (HOLLAND) BV WESTERDUINWEG 3 1755 LE PETTEN NETHERLANDS
US Philips Corp
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US Philips Corp
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Assigned to MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDUINWEG 3, 1755 LE PETTEN, THE NETHERLANDS reassignment MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDUINWEG 3, 1755 LE PETTEN, THE NETHERLANDS CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE DATE: SEPTEMBER 3, 1984 Assignors: BYK-MALLINCKRODT CIL B.V.
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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
    • A61K51/12—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
    • A61K51/1203—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 in a form not provided for by groups A61K51/1206 - A61K51/1296, e.g. cells, cell fragments, viruses, virus capsides, ghosts, red blood cells, viral vectors
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • 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

  • the invention relates to a method of producing a carrier for a scintigraphic preparation in which red blood corpuscles are sensitized by treatment with a stannous chloride solution.
  • the invention also relates to a method of producing a scintigraphic preparation in which tin-sensitized red blood corpuscles are labelled with radioactive pertechnetate. 7
  • the invention provides a carrier by means of which scintigraphic preparations are obtainable in which the labelling efficiency is 90 percent. Obviously this is an important'practical and economic improvement: the volume of the scintigraphic preparation to be administered to a patient can be reduced to one third; the losses of radio-active material have been reduced to one seventh.
  • the said improved efficiency is achieved by sensitizing the red blood corpuscles by means of a stannous chloride solution buffered to a physiological pH (about 7.4).
  • the invention thus relates to a method of producing a carrier for a scintigraphic preparation in which red blood corpuscles are sensitized by treatment with a stannous chloride solution characterized in that a stannous chloride solution is used that is buffered to a physiological pH. 7
  • the invention also relates to a method of producing a scintigraphic preparation in which red blood corpuscles are sensitized by mea'ns'of a stannous chloride solution and then labelled with radio-active pertechnetate, which method is characterized in that for the sensitizing operation a stannous chloride solution buffered to a physiological pH is used.
  • any physiologically acceptable buffers may be used, such as alkali citrates, alkali tartrates, alkali phosphates, and the like.
  • Sensitization is effected by stirring a suspension of red blood corpuscles in a buffered stannous chloride solution for a short time, for example one or a few minutes. The excess of stannous ions is then removed. This may be performed by centrifuging the suspension and stirring the sediment in a washing liquid, which then is again centrifuged.
  • the washing liquid may be a physiological salt solution.
  • the excess of stannous ions may, however, be removed more effectively by adding a complex binder, for example ethylene diamine tetraacetic acid disodium salt (EDTA), either to the original suspension or to the washing liquid.
  • EDTA ethylene diamine tetraacetic acid disodium salt
  • the amount of stannous chloride required for sensitization may vary within comparatively wide limits without appreciably influencing the labelling efficiency. As a rule, from 0.03 to 1.5 mg of SnCl per 10 ml of blood is used.
  • the red blood corpuscles may be radio-actively labelled, for example by means of pertechnetate, with out the labelling efficiency being affected. Labelling may be performed, for example, by a method as described in French Pat. 1,518,139.
  • the carrier may be packaged in bottles or injection syringes by conventional techniques.
  • the radio-active labelling is preferably effected immediately prior to the use of the preparation.
  • the scintigraphic preparation can be used for blood tests, examination of the spleen, the heart, the brain, the blood vessels, and the like.
  • EXAMPLE a 10 g of stannous chloride was dissolved in 1 ml of 10 N hydrochloric acid. The solution was added drop by drop to a solution of 2.715 g of trisodium citrate in 30 ml of distilled water. The volume was increased to ml with distilled water, after which sodium hydroxide (about 3.5 ml) was added until the pH of the solution was 7.4.
  • the sediment was taken up in 10 ml of a physiological salt solution, stirred and again sedimentated by centrifuging. Finally the sediment was again taken up in a physiological salt solution.
  • the ready product has an activity of 700 p.C.
  • a method of producing a carrier for a scintigraphic preparation comprising subjecting red blood corpuscles to the action of a stannous chloride solution buffered to a physiological pH in an amount of, from 0.03 to 1.5 mg of stannous chloride per 10 ml of blood, and removing any excess of stannous ions.
  • a method of producing a scintigraphic preparation comprising subjecting red blood corpuscles to the action of a stannous chloride solution buffered to a physiological pH, in an amount of from 0.03 mg to 1.5 mg of stannous chloride per 100 ml of blood, removing any excess of stannous ions and then treating said red blood corpuscles with a pertechnetate thereby radioactively labelling said red corpuscles.
  • a carrier for a scintigraphic preparation obtained by the method of claim I.

Abstract

Scintigraphic carriers are obtained by sensitizing red blood corpuscles by means of a stannous chloride solution having a physiological pH. The carriers are then labelled with radioactive pertechnetate. The labelling efficiency is appreciably higher than in the known methods.

Description

States-Patent 91 METHOD OF PRODUCING A CARRIER FOR A SCINTIGRAPI-IIC PREPARATION AND SCINTIGRAPIIIC PREPARATIONS INCLUDING SAID CARRIER Inventor: Jean-Paul Nouel, Boisguillaume,
France Assignee: U.S. Philips Corporation, New
York, NY.
Filed: May 1, 1970 Appl. No.: 33,989
Foreign Application Priority Data May 5, 1969 France 6914129 U.S. Cl. 424/1, 250/106 T, 252/30l.l R,
250/715 5,424/131, 424/288, Int. Cl A6lk 27/04 Field of Search 424/1, 11, 101,131, 288; 252/301.l R; 23/230 B; 250/106 T, 71.5 S
[111' 3,812,264 [451 May 21, 1974 [56] References Cited OTHER PUBLICATIONS Morcellet et al., Nuclear Sci. Abstracts, Vol. 24, No. 4, p. 617 No. 6078-Abstract from J. Biol. Med. Nucl: 4, No. 17, 16-18 (May-June 1969). 1 Journal de Biologie et de Midicine Nucleare A.T.E.N., Vol. IV, No. 15 pp. 20-24 (1969).
Primary Examiner-Benjamin R. Padgett Attorney, Agent, or Firm-Norman N. Spain; Frank R. Trifari 5 7 ABSTRACT 5 Claims, No Drawings The invention relates to a method of producing a carrier for a scintigraphic preparation in which red blood corpuscles are sensitized by treatment with a stannous chloride solution. The invention also relates to a method of producing a scintigraphic preparation in which tin-sensitized red blood corpuscles are labelled with radioactive pertechnetate. 7
From Journal de Biologie et de Medicine Nucleaires A.T.E.N., vol. N, no. 15, pages 2024 (1969) it is known to produce a carrier for a scintigraphic preparation and to produce a scintigraphic preparation using this carrier by mixing blood with a 1 percent heparine solution and then centrifuging. The red blood corpuscles are subsequently suspensed in a medium consisting of a physiological salt solution, plasma gel and stannous chloride. The sensitized red blood corpuscles then are isolated according to known methods by centrifuging, after which they are brought into contact with radioactive pertechnetate. After a contact time of 30 minutes, they are again centrifuged and washed four times with a physiological salt solution. After resuspending in a physiological salt solution the preparation is ready for use. The labelling efficiency is 30 percent.
The invention provides a carrier by means of which scintigraphic preparations are obtainable in which the labelling efficiency is 90 percent. Obviously this is an important'practical and economic improvement: the volume of the scintigraphic preparation to be administered to a patient can be reduced to one third; the losses of radio-active material have been reduced to one seventh.
The said improved efficiency is achieved by sensitizing the red blood corpuscles by means of a stannous chloride solution buffered to a physiological pH (about 7.4).
The invention thus relates to a method of producing a carrier for a scintigraphic preparation in which red blood corpuscles are sensitized by treatment with a stannous chloride solution characterized in that a stannous chloride solution is used that is buffered to a physiological pH. 7
The invention also relates to a method of producing a scintigraphic preparation in which red blood corpuscles are sensitized by mea'ns'of a stannous chloride solution and then labelled with radio-active pertechnetate, which method is characterized in that for the sensitizing operation a stannous chloride solution buffered to a physiological pH is used.
As buffers any physiologically acceptable buffers may be used, such as alkali citrates, alkali tartrates, alkali phosphates, and the like.
Sensitization is effected by stirring a suspension of red blood corpuscles in a buffered stannous chloride solution for a short time, for example one or a few minutes. The excess of stannous ions is then removed. This may be performed by centrifuging the suspension and stirring the sediment in a washing liquid, which then is again centrifuged. The washing liquid may be a physiological salt solution. The excess of stannous ions may, however, be removed more effectively by adding a complex binder, for example ethylene diamine tetraacetic acid disodium salt (EDTA), either to the original suspension or to the washing liquid.
The amount of stannous chloride required for sensitization may vary within comparatively wide limits without appreciably influencing the labelling efficiency. As a rule, from 0.03 to 1.5 mg of SnCl per 10 ml of blood is used.
Within a period of 9 days after the preparation of the carrier, the red blood corpuscles maybe radio-actively labelled, for example by means of pertechnetate, with out the labelling efficiency being affected. Labelling may be performed, for example, by a method as described in French Pat. 1,518,139.
The carrier may be packaged in bottles or injection syringes by conventional techniques. The radio-active labelling is preferably effected immediately prior to the use of the preparation.
The scintigraphic preparation can be used for blood tests, examination of the spleen, the heart, the brain, the blood vessels, and the like.
EXAMPLE a. 10 g of stannous chloride was dissolved in 1 ml of 10 N hydrochloric acid. The solution was added drop by drop to a solution of 2.715 g of trisodium citrate in 30 ml of distilled water. The volume was increased to ml with distilled water, after which sodium hydroxide (about 3.5 ml) was added until the pH of the solution was 7.4.
1 ml of the resulting solution was added to 10 ml of venous blood. The mixture was stirred for 1 minute, after which 1 ml of a 5 percent ethylene diamine tetraacetic acid disodium salt solution was added. After stirring again for 1 minute the liquid was centrifuged.
The sediment was taken up in 10 ml of a physiological salt solution, stirred and again sedimentated by centrifuging. Finally the sediment was again taken up in a physiological salt solution.
b. The preparation obtained by the method described in a) was radio-actively labelled with sodium pertechnetate by stirring it together with 1 ml of a pertechnetate solution taken from the radio-active milker for 20 minutes. The mixture was centrifuged and the sediment resuspended in 10 ml of a physiological salt solution, which treatment was repeated thrice.
The ready product has an activity of 700 p.C.
lt should be noted that the entire processing was effected under aseptic conditions.
What is claimed is:
l. A method of producing a carrier for a scintigraphic preparation, said method comprising subjecting red blood corpuscles to the action of a stannous chloride solution buffered to a physiological pH in an amount of, from 0.03 to 1.5 mg of stannous chloride per 10 ml of blood, and removing any excess of stannous ions.
2. A method of producing a scintigraphic preparation comprising subjecting red blood corpuscles to the action of a stannous chloride solution buffered to a physiological pH, in an amount of from 0.03 mg to 1.5 mg of stannous chloride per 100 ml of blood, removing any excess of stannous ions and then treating said red blood corpuscles with a pertechnetate thereby radioactively labelling said red corpuscles.
3. The method of claim 1 wherein trisodium citrate is used as a buffer.
4. A carrier for a scintigraphic preparation obtained by the method of claim I.
5. A scintigraphic preparation obtained by the method of claim 1.
mg UNITED STATES PATENT OFFICE v 1 I CERTIFICATE OF CORRECTION Patent No. 3,312,264 Dated May 21,1974
Inventor(s) Q EAE -PAUL NOUEL It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
In the title page, Item [30], "6914129' should be 69l4l79 Signed and sealed this 24th day of September 1974.
(SEAL) Attest:
McCOY M. GIBSON. JR. c. MARSHALL DANN Attesting Officer -1' Commissioner of Patents 133 UNITED STATES PATENT OFFICE v CERTIFICATE OF CORRECTION pm: No. 3,812,264 Dated May 21, 1974 Inventofls) JEAN-PAUL NOUEL It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
In the title page, Item [30] "6914129" should be 6914179 T Signed and sealed this 24th day of September 1974.
(SEAL) Attest:
McCOY M. GIBSON JR; MARSHALL DANN Attesting Officer Commissioner of Patents

Claims (4)

  1. 2. A method of producing a scintigraphic preparation comprising subjecting red blood corpuscles to the action of a stannous chloride solution buffered to a physiological pH, in an amount of from 0.03 mg to 1.5 mg of stannous chloride per 100 ml of blood, removing any excess of stannous ions and then treating said red blood corpuscles with a pertechnetate thereby radioactively labelling said red corpuscles.
  2. 3. The method of claim 1 wherein trisodium citrate is used as a buffer.
  3. 4. A carrier for a scintigraphic preparation obtained by the method of claim 1.
  4. 5. A scintigraphic preparation obtained by the method of claim
US00033989A 1969-05-05 1970-05-01 Method of producing a carrier for a scintigraphic preparation and scintigraphic preparations including said carrier Expired - Lifetime US3812264A (en)

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JP (1) JPS5022088B1 (en)
BE (1) BE749922A (en)
CH (1) CH540693A (en)
DE (1) DE2020348C3 (en)
FR (1) FR2043459A1 (en)
GB (1) GB1313165A (en)
NL (1) NL7006244A (en)
SE (1) SE360562B (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4372294A (en) * 1980-09-25 1983-02-08 The Massachusetts General Hospital Method and apparatus for radiolabeling red blood cells
EP0179481A2 (en) * 1984-10-26 1986-04-30 Nihon Medi-Physics Co., Ltd. Stable stannous chloride composition for labeling with radioactive technetium
US5277892A (en) * 1990-08-08 1994-01-11 Rhomed Incorporated In vivo lymphocyte tagging
US5277893A (en) * 1989-08-09 1994-01-11 Rhomed, Incorporated Direct radiolabeling of substrates containing monosulfides or disulfide bonds with radionuclides
US5346687A (en) * 1989-08-09 1994-09-13 Rhomed Incorporated Direct radiolabeling of antibody against stage specific embryonic antigen for diagnostic imaging
US5443816A (en) * 1990-08-08 1995-08-22 Rhomed Incorporated Peptide-metal ion pharmaceutical preparation and method
US5460785A (en) * 1989-08-09 1995-10-24 Rhomed Incorporated Direct labeling of antibodies and other protein with metal ions
US5643549A (en) * 1992-02-20 1997-07-01 Rhomed Incorporated Leukostimulatory agent for in vivo leukocyte tagging

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4372294A (en) * 1980-09-25 1983-02-08 The Massachusetts General Hospital Method and apparatus for radiolabeling red blood cells
EP0179481A2 (en) * 1984-10-26 1986-04-30 Nihon Medi-Physics Co., Ltd. Stable stannous chloride composition for labeling with radioactive technetium
EP0179481A3 (en) * 1984-10-26 1988-03-02 Nihon Medi-Physics Co., Ltd. Stable stannous chloride composition for labeling with radioactive technetium
US4880616A (en) * 1984-10-26 1989-11-14 Nihon Medi-Physics Co., Ltd Stable stannous chloride composition for labeling with radioactive technetium
US5015462A (en) * 1984-10-26 1991-05-14 Nihon Medi-Physics Co. Ltd. Stable stannous chloride composition for labeling with radioactive technetium
US5096693A (en) * 1984-10-26 1992-03-17 Nihon Medi-Physics Co., Ltd. Stable stannous chloride composition for labeling with radioactive technetium
US5460785A (en) * 1989-08-09 1995-10-24 Rhomed Incorporated Direct labeling of antibodies and other protein with metal ions
US5277893A (en) * 1989-08-09 1994-01-11 Rhomed, Incorporated Direct radiolabeling of substrates containing monosulfides or disulfide bonds with radionuclides
US5346687A (en) * 1989-08-09 1994-09-13 Rhomed Incorporated Direct radiolabeling of antibody against stage specific embryonic antigen for diagnostic imaging
US5861139A (en) * 1989-08-09 1999-01-19 Rhodes; Buck A. Direct labeling of peptides with metal ions
US5277892A (en) * 1990-08-08 1994-01-11 Rhomed Incorporated In vivo lymphocyte tagging
US5690905A (en) * 1990-08-08 1997-11-25 Rhomed Incorporated Peptide-metal ion pharmaceutical labeling method
US5759516A (en) * 1990-08-08 1998-06-02 Rhomed Incorporated Peptide-metal ion pharmaceutical preparation
US5443816A (en) * 1990-08-08 1995-08-22 Rhomed Incorporated Peptide-metal ion pharmaceutical preparation and method
US5643549A (en) * 1992-02-20 1997-07-01 Rhomed Incorporated Leukostimulatory agent for in vivo leukocyte tagging

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GB1313165A (en) 1973-04-11
BE749922A (en) 1970-11-04
JPS5022088B1 (en) 1975-07-28
CH540693A (en) 1973-08-31
DE2020348A1 (en) 1970-11-19
DE2020348B2 (en) 1979-08-23
DE2020348C3 (en) 1980-04-30
SE360562B (en) 1973-10-01
FR2043459A1 (en) 1971-02-19
NL7006244A (en) 1970-11-09

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