EP0000253A1 - Diagnostic kit for blood pool imaging - Google Patents

Diagnostic kit for blood pool imaging Download PDF

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Publication number
EP0000253A1
EP0000253A1 EP78300048A EP78300048A EP0000253A1 EP 0000253 A1 EP0000253 A1 EP 0000253A1 EP 78300048 A EP78300048 A EP 78300048A EP 78300048 A EP78300048 A EP 78300048A EP 0000253 A1 EP0000253 A1 EP 0000253A1
Authority
EP
European Patent Office
Prior art keywords
stannous
salt
chloride dihydrate
glucoheptonate
stannous chloride
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP78300048A
Other languages
German (de)
French (fr)
Other versions
EP0000253B1 (en
Inventor
Paul-Emile Bonneau
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Organon Pharma UK Ltd
Merck Sharp and Dohme IA Corp
Original Assignee
Merck Sharp and Dohme Ltd
Merck Sharp and Dohme IA Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Sharp and Dohme Ltd, Merck Sharp and Dohme IA Corp filed Critical Merck Sharp and Dohme Ltd
Publication of EP0000253A1 publication Critical patent/EP0000253A1/en
Application granted granted Critical
Publication of EP0000253B1 publication Critical patent/EP0000253B1/en
Expired legal-status Critical Current

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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
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • 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
    • 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

  • One of the methods employed in the past to image the blood pool for diagnostic purposes involves the intravenous administration of 99m Tc serum albumin which is available commercially and is a sterile pyrogen-free solution of albumin labelled with Technetium 99m having an activity of greater than 100 microcuries/ml.
  • Another method used in the past for imaging blood pools is the in vitro labelling of red blood cells (outside the host animal) followed by reinjection of the cells into the vascular system of the selected animal.
  • this method it is possible to visualize both heart blcod pools plus major peripheral vessels up to 3 hours after injection of the labelled cells. As can be seen, this is a complicated procedure, and therefore is a more time- consuming and expensive method.
  • Still another procedure for imaging blood involves the injection of stannous pyrophosphate followed by injection of 99m Tc-pertechnetate. This technique is reported as successful in producing satisfactory imaging of blood pools.
  • a diagnostic kit suitable for the radioactive labelling of red blood cells in vivo, thus making possible the imaging of blood pools within the circulatory system of the patient being examined.
  • a novel chemical composition comprising a lyophilized mixture of a glucoheptonate salt and a pharmaceutically acceptable stannous salt in the ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt measured as calcium glucoheptonate and stannous chloride dihydrate or approximately 22.9 parts of glucoheptonate ion to 1.32 parts of tin calculated as available stannous ion.
  • An important feature of the present invention is the provision of an individual diagnostic kit containing a non-toxic stannous salt capable of supplying an amount of stannous ion equivalent to no more than 4.0 mg and preferably at least 2.5 mg of stannous chloride dihydrate. Less than 2.5 mg of the stannous chloride does not provide sufficient stannous ion to effect a satisfactory degree of labelling of red blood cells. Because of the known toxicity of stannous salts, no more than 4 mg of stannous chloride dihydrate or a stannous salt containing an equivalent amount of stannous ion should be incorporated in an individual dosage kit.
  • the present invention also includes the process for the preparation of the novel chemical composition and the diagnostic method for imagine blood pools in patients suspected of having abnormalities in the circulatory system.
  • a sterile solution of a non-toxic, pharmaceutically acceptable salt of glucoheptonic acid e.g., calcium glucoheptonate
  • a non-toxic stannous salt in a ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt, calculated as calcium glucoheptonate and stannous chloride dihydrate.
  • the solution is adjusted to a neutral pH 6-8, subdivided, and lyophilized to produce individual vials containing a dry, sterile mixture comprising 25 mg. calcium glucoheptonate and 3 mg. stannous chloride ⁇ dihydrate.
  • a vial containing the dry, sterile mixture of calcium glucoheptonate and stannous chloride dihydrate is reconstituted by mixing with 2-8 ml. of a USP saline solution.
  • the reconstituted solution is then used for injection of the patient to be examined.
  • a second injection of 2-8 ml. of a sterile saline solution of sodium pertechnetate is made.
  • Following the injection of sodium pertechnetate it is possible, after waiting from 30 seconds to 2 minutes, to image the blood pools in the patient being.examined.
  • a solution is prepared under sterile conditions with 25 g. of calcium glucoheptonate in sterile, pyrogen-free water which has been purged with nitrogen.
  • the solution of calcium glucoheptonate is stored and purged under nitrogen.
  • 3 g. of stannous chloride dihydrate is dissolved in 1 ml. of hydrochloric acid, and the resulting solution diluted with nitrogen-purged, sterile water to a volume of 10 ml.
  • the stannous chloride dihydrate solution is then added to the calcium glucoheptonate with stirring and flushing with nitrogen.
  • the solution is mixed thoroughly, and the pH is adjusted to neutrality with a solution of sterile IN sodium hydroxide solution.
  • the volume is then adjusted to 2000 ml.
  • each. vial contains 25 mg. of calcium glucoheptonate and 3 mg. of stannous chloride dihydrate.
  • a solution of sodium chloride for injection USP (2 ml.) is added to a vial containing a lyophilized mixture of 3 mg. of stannous chloride dihydrate and 25.0 mg. calcium glucoheptonate.
  • the resulting solution is used for the intravenous injection of patients for the purpose of imaging the blood pools for diagnostic purposes.
  • the amount of solution used is based on the weight of the patient and sufficient volume is used so that 30 mcg./kg. of stannous ion, measured as stannous chloride dihydrate, is injected. It is recommended that no more than the contents of one vial be administered to any patient.
  • a sterile saline solution of sodium p ertech- netate - Tc99m (2-20 mCi) is injected. This tags the red blood cells and permits imaging of the blood pools of the patient being examined almost immediately (from 30 seconds to 2 minutes).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

This invention relates to a method for efficiently labelling red blood cells, which permits the imaging of blood pools in the intact animal or human patient, accomplished by injection of a saline solution of an alkaline earth metal salt of glucoheptonic acid and a non-toxic stannous salt followed by injection with a solution of sodium pertechnetate Tc 99m to tag the red blood cells.
The invention also relates to the kit used in the method of our invention, consisting of a single vial containing a lyophilized mixture of 25 mg. of calcium glucoheptonate and 3 mg. of stannous chloride dihydrate in 2 ml. of saline solution.

Description

    BACKGROUND OF THE INVENTION
  • One of the methods employed in the past to image the blood pool for diagnostic purposes involves the intravenous administration of 99m Tc serum albumin which is available commercially and is a sterile pyrogen-free solution of albumin labelled with Technetium 99m having an activity of greater than 100 microcuries/ml.
  • In utilizing this method of blood pool imaging, it is important to predose the patient immediately prior to the attempted visualization of the blood pool, since the 99m Tc serum albumin is very rapidly lost from the blood stream by exchange in the kidney.
  • Another method used in the past for imaging blood pools is the in vitro labelling of red blood cells (outside the host animal) followed by reinjection of the cells into the vascular system of the selected animal. By this method, it is possible to visualize both heart blcod pools plus major peripheral vessels up to 3 hours after injection of the labelled cells. As can be seen, this is a complicated procedure, and therefore is a more time- consuming and expensive method.
  • Still another procedure for imaging blood involves the injection of stannous pyrophosphate followed by injection of 99m Tc-pertechnetate. This technique is reported as successful in producing satisfactory imaging of blood pools.
  • In accordance with the present invention, there is provided a diagnostic kit suitable for the radioactive labelling of red blood cells in vivo, thus making possible the imaging of blood pools within the circulatory system of the patient being examined. As an integral part of the diagnostic kit of the present invention, there is also provided a novel chemical composition comprising a lyophilized mixture of a glucoheptonate salt and a pharmaceutically acceptable stannous salt in the ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt measured as calcium glucoheptonate and stannous chloride dihydrate or approximately 22.9 parts of glucoheptonate ion to 1.32 parts of tin calculated as available stannous ion.
  • An important feature of the present invention is the provision of an individual diagnostic kit containing a non-toxic stannous salt capable of supplying an amount of stannous ion equivalent to no more than 4.0 mg and preferably at least 2.5 mg of stannous chloride dihydrate. Less than 2.5 mg of the stannous chloride does not provide sufficient stannous ion to effect a satisfactory degree of labelling of red blood cells. Because of the known toxicity of stannous salts, no more than 4 mg of stannous chloride dihydrate or a stannous salt containing an equivalent amount of stannous ion should be incorporated in an individual dosage kit.
  • The present invention also includes the process for the preparation of the novel chemical composition and the diagnostic method for imagine blood pools in patients suspected of having abnormalities in the circulatory system.
  • In accordance with the process of the present invention, a sterile solution of a non-toxic, pharmaceutically acceptable salt of glucoheptonic acid, e.g., calcium glucoheptonate, is mixed with a non-toxic stannous salt in a ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt, calculated as calcium glucoheptonate and stannous chloride dihydrate.
  • The solution is adjusted to a neutral pH 6-8, subdivided, and lyophilized to produce individual vials containing a dry, sterile mixture comprising 25 mg. calcium glucoheptonate and 3 mg. stannous chloride·dihydrate.
  • In utilizing the kit of the present invention for imaging the blood pools of a patient to diagnose abnormalities.in the cardiovascular system, a vial containing the dry, sterile mixture of calcium glucoheptonate and stannous chloride dihydrate is reconstituted by mixing with 2-8 ml. of a USP saline solution. The reconstituted solution is then used for injection of the patient to be examined. After a period of 30 minutes, a second injection of 2-8 ml. of a sterile saline solution of sodium pertechnetate is made. Following the injection of sodium pertechnetate, it is possible, after waiting from 30 seconds to 2 minutes, to image the blood pools in the patient being.examined. This "in vivo" labeling of the red blood cells is exceptionally stable and approximately 95% of the radioactivity is retained by the red blood cells for at least 6 hours following injection. This simple procedure avoids the instability of the human serum albumin/99m Tc injection of the prior art as well as the expense and inconvenience of the in vitro labeling of the red blood cells noted as an alternate prior art method.
    • EXAMPLE 1 Blood Pool Imaging Kit
  • A solution is prepared under sterile conditions with 25 g. of calcium glucoheptonate in sterile, pyrogen-free water which has been purged with nitrogen. The solution of calcium glucoheptonate is stored and purged under nitrogen. In a separate container, 3 g. of stannous chloride dihydrate is dissolved in 1 ml. of hydrochloric acid, and the resulting solution diluted with nitrogen-purged, sterile water to a volume of 10 ml. The stannous chloride dihydrate solution is then added to the calcium glucoheptonate with stirring and flushing with nitrogen. The solution is mixed thoroughly, and the pH is adjusted to neutrality with a solution of sterile IN sodium hydroxide solution. The volume is then adjusted to 2000 ml. with sterile, nitrogen-purged water and subdivided into vials, each containing 2 ml. of the solution. The vials are then lyophilized and sealed under nitrogen. Each. vial contains 25 mg. of calcium glucoheptonate and 3 mg. of stannous chloride dihydrate.
    • EXAMPLE 2 Method of Using Blood Pool Imaging Kit
  • A solution of sodium chloride for injection USP (2 ml.) is added to a vial containing a lyophilized mixture of 3 mg. of stannous chloride dihydrate and 25.0 mg. calcium glucoheptonate. The resulting solution is used for the intravenous injection of patients for the purpose of imaging the blood pools for diagnostic purposes. The amount of solution used is based on the weight of the patient and sufficient volume is used so that 30 mcg./kg. of stannous ion, measured as stannous chloride dihydrate, is injected. It is recommended that no more than the contents of one vial be administered to any patient. After waiting a period of 30 minutes, a sterile saline solution of sodium pertech- netate-Tc99m (2-20 mCi) is injected. This tags the red blood cells and permits imaging of the blood pools of the patient being examined almost immediately (from 30 seconds to 2 minutes).

Claims (10)

1 A diagnostic kit used for blood pool imaging comprising a sterile sealed vial containing a lyophilized mixture of a non-toxic pharmaceutically acceptable salt of glucoheptonic acid and a non-toxic pharmaceutically acceptable stannous salt in a ratio of 22.9 parts by weight of glucoheptonate ion to 1.32 parts of stannous ion, provided that the individual dose of stannous ion does not exceed 4 mg, calculated as stannous chloride dihydrate.
2 A kit according to claim 1 in which the salt of glucoheptonic acid is calcium glucoheptonate and the stannous salt is stannous chloride dihydrate.
3 A kit according to claim 2 in which the lyophilized mixture comprises from 2.5-4 mg of stannous chloride dihydrate and 25 mg of calcium glucoheptonate.
4 A kit according to claim 3 that comprises a lyophilized mixture of 3 mg of stannous chloride dihydrate and 25 mg of calcium glucoheptonate.
5 A process for the preparation of a blood pool imaging kit that comprises preparing a sterile aqueous solution of a water-soluble non-toxic pharmaceutically acceptable salt of glucoheptonic acid and a non-toxic pharmaceutically acceptable stannous salt, subdividing the said solution into individual dose vials under nitrogen, and lyophilizing and sealing the said vials under nitrogen, in which the individual dose of stannous ion does not exceed 4 mg, calculated as stannous chloride dihydrate, and there is 22.9 parts by weight of glucoheptonate ion to 1.32 parts of stannous ion.
6 A process according to claim 5 in which the glucoheptonate salt is calcium glucoheptonate and the stannous salt is stannous chloride dihydrate.
7 A process according to claim 6 in which the individual dose vials contain from 2.5-4 mg of stannous salt calculated as stannous chloride dihydrate and 25 mg of calcium glucoheptonate.
8 A process according to claim 7 in which the individual dose vials contain 3 mg of stannous salt, calculated as stannous chloride dihydrate, and 25 mg of calcium glucoheptonate.
9 A method of imaging blood pools in patients suspected of having cardiovascular abnormalities which comprises the steps of
(1) intravenous injection of a solution comprising a water soluble, non-toxic, pharmaceutically acceptable salt of ketoglucoheptcnic acid and a water soluble non-toxic stannous salt in the ratio set forth in claim 1, provided that the individual dose of stannous ion does not exceed 4 mg, calculated as stannous chloride dihydrate,
(2) waiting a period of 30 minutes; and
(3) intravenous injection of a sterile saline solution containing from 2-20 mCi of sodium pertechnetate-Tc99m.
10 A method according to claim 9 in which the glucoheptonate salt used is calcium glucoheptonate and the stannous salt is stannous chloride dihydrate.
EP78300048A 1977-06-17 1978-06-15 Diagnostic kit for blood pool imaging Expired EP0000253B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CA280,764A CA1105815A (en) 1977-06-17 1977-06-17 Red blood cell labelling kit
CA280764 1977-06-17

Publications (2)

Publication Number Publication Date
EP0000253A1 true EP0000253A1 (en) 1979-01-10
EP0000253B1 EP0000253B1 (en) 1981-10-28

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US (1) US4300569A (en)
EP (1) EP0000253B1 (en)
JP (1) JPS5417129A (en)
CA (1) CA1105815A (en)
DE (1) DE2861257D1 (en)
DK (1) DK269578A (en)
IE (1) IE47091B1 (en)
IT (1) IT1105145B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU704591B2 (en) * 1994-04-04 1999-04-29 William R. Freeman Use of phosphonylmethoxyalkyl nucleosides for the treatment of raised intraocular pressure
DE102007053722A1 (en) 2007-11-10 2009-05-20 Amphenol-Tuchel Electronics Gmbh Hermaphroditic connector
US7803970B2 (en) 2002-02-28 2010-09-28 University Of Tennessee Research Foundation Multi-substitued selective androgen receptor modulators and methods of use thereof

Families Citing this family (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
US4443426A (en) * 1982-06-14 1984-04-17 Yale University Blood agent
US4581221A (en) * 1983-08-29 1986-04-08 Medi Nuclear Corporation, Inc. Ulcer detection
US4755375A (en) * 1984-01-27 1988-07-05 Associated Universities, Inc. Method and kit for the selective labeling of red blood cells in whole blood with TC-99M
JPS61103841A (en) * 1984-10-26 1986-05-22 Nippon Mejifuijitsukusu Kk Stable stannous chloride composition to be fed radioactivity technetium mark
US4789541A (en) * 1985-10-04 1988-12-06 Davis Michael H Method and composition for in vivo radiolabeling of red blood cells with 99m Tc
US4692324A (en) * 1985-10-04 1987-09-08 Davis Michael H Method and composition for in vivo radiolabeling of red blood cells with 99m Tc
US5529189A (en) * 1995-08-02 1996-06-25 Daxor Corporation Syringe assembly for quantitative measurement of radioactive injectate and kit having same

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4027005A (en) * 1974-06-07 1977-05-31 New England Nuclear Corporation Diagnostic agents

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3743714A (en) * 1970-12-04 1973-07-03 Cis Radiopharmaceuticals Inc Novel carrier preparations for injectable radioactive compositions
CA1027135A (en) * 1973-06-11 1978-02-28 Research Corporation Bone-seeking technetium-99m complex
US4042677A (en) * 1974-08-29 1977-08-16 Union Carbide Corporation Technetium-99m labeled radiodiagnostic agents and method of preparation
GB1535847A (en) * 1976-03-19 1978-12-13 Radiochemical Centre Ltd Technetium-99m labelled tin colloid for body scanning
US4054645A (en) * 1976-08-24 1977-10-18 Minnesota Mining And Manufacturing Company Radiodiagnostic complexes employing fluorine-containing tin reducing agents
US4070493A (en) * 1977-03-16 1978-01-24 Merck & Co., Inc. Diagnostic kit

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4027005A (en) * 1974-06-07 1977-05-31 New England Nuclear Corporation Diagnostic agents

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 85, Ref 137277v (1976) *
CHEMICAL ABSTRACTS, vol. 86, Ref. 152115e (1977) *
JOURNAL OF NUCLEAR MEDICINE, vol. 16, pages 357 to 367 (1975) *
JOURNAL OF NUCLEAR MEDICINE, vol. 16, pages 875 to 878 (1975) *
JOURNAL OF NUCLEAR MEDICINE, vol. 17, pages 203-207 (1976) *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU704591B2 (en) * 1994-04-04 1999-04-29 William R. Freeman Use of phosphonylmethoxyalkyl nucleosides for the treatment of raised intraocular pressure
US7803970B2 (en) 2002-02-28 2010-09-28 University Of Tennessee Research Foundation Multi-substitued selective androgen receptor modulators and methods of use thereof
DE102007053722A1 (en) 2007-11-10 2009-05-20 Amphenol-Tuchel Electronics Gmbh Hermaphroditic connector

Also Published As

Publication number Publication date
IE781195L (en) 1978-12-17
IT1105145B (en) 1985-10-28
DE2861257D1 (en) 1982-01-07
US4300569A (en) 1981-11-17
CA1105815A (en) 1981-07-28
DK269578A (en) 1978-12-18
EP0000253B1 (en) 1981-10-28
IE47091B1 (en) 1983-12-14
JPS6315248B2 (en) 1988-04-04
IT7849830A0 (en) 1978-06-12
JPS5417129A (en) 1979-02-08

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