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Publication numberUS3812264 A
Publication typeGrant
Publication dateMay 21, 1974
Filing dateMay 1, 1970
Priority dateMay 5, 1969
Also published asDE2020348A1, DE2020348B2, DE2020348C3
Publication numberUS 3812264 A, US 3812264A, US-A-3812264, US3812264 A, US3812264A
InventorsNouel J
Original AssigneePhilips Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Method of producing a carrier for a scintigraphic preparation and scintigraphic preparations including said carrier
US 3812264 A
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Description  (OCR text may contain errors)

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

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4372294 *Sep 25, 1980Feb 8, 1983The Massachusetts General HospitalMethod and apparatus for radiolabeling red blood cells
US4880616 *Dec 17, 1987Nov 14, 1989Nihon Medi-Physics Co., LtdMedical diagnosis
US5015462 *Jun 8, 1989May 14, 1991Nihon Medi-Physics Co. Ltd.Medical diagnosis for blood
US5096693 *Feb 15, 1991Mar 17, 1992Nihon Medi-Physics Co., Ltd.Dissolving stannous chloride in aqueous solvent, charging to c ontainer, freeze drying, sealing; diagnostic agent
US5277892 *Feb 20, 1992Jan 11, 1994Rhomed IncorporatedAdministering a mixture of a lectin and a linked imaging ion
US5277893 *Apr 6, 1992Jan 11, 1994Rhomed, IncorporatedDirect radiolabeling of substrates containing monosulfides or disulfide bonds with radionuclides
US5346687 *Jan 3, 1992Sep 13, 1994Rhomed IncorporatedPartial reduction of disulfide bonds with stannous compound
US5443816 *Feb 20, 1992Aug 22, 1995Rhomed IncorporatedPeptide-metal ion pharmaceutical preparation and method
US5460785 *Jan 3, 1992Oct 24, 1995Rhomed IncorporatedDirect labeling of antibodies and other protein with metal ions
US5643549 *Jan 11, 1994Jul 1, 1997Rhomed IncorporatedLeukostimulatory agent for in vivo leukocyte tagging
US5690905 *May 31, 1995Nov 25, 1997Rhomed IncorporatedPeptide-metal ion pharmaceutical labeling method
US5759516 *May 31, 1995Jun 2, 1998Rhomed IncorporatedPeptide-metal ion pharmaceutical preparation
US5861139 *Jun 5, 1995Jan 19, 1999Rhodes; Buck A.Method and composition for labeling proteins, peptides and amino acids, including antibodies, with a variety of metals ions (tin), including radioisotopes
EP0179481A2 *Oct 24, 1985Apr 30, 1986Nihon Medi-Physics Co., Ltd.Stable stannous chloride composition for labeling with radioactive technetium
Classifications
U.S. Classification424/1.17, 250/303, 556/107, 435/317.1, 534/14, 250/493.1, 424/650
International ClassificationA61K51/12, A61K51/00, G01N33/60, G01N33/50, G21H5/00
Cooperative ClassificationA61K2123/00, A61K51/12, G01N33/50, A61K51/1203
European ClassificationG01N33/50, A61K51/12, A61K51/12A
Legal Events
DateCodeEventDescription
Oct 2, 1985AS01Change of name
Owner name: BYK-MALLINCKRODT CIL B.V.
Owner name: MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDU
Effective date: 19850728
Oct 2, 1985ASAssignment
Owner name: MAALLINCKRODT DIAGNOSTICA (HOLLAND) B.V., WESTERDU
Free format text: CHANGE OF NAME;ASSIGNOR:BYK-MALLINCKRODT CIL B.V.;REEL/FRAME:004466/0151
Effective date: 19850728