US3812245A - Novel compositions for radiotracer localization of deep vein thrombi - Google Patents

Novel compositions for radiotracer localization of deep vein thrombi Download PDF

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Publication number
US3812245A
US3812245A US00282100A US28210072A US3812245A US 3812245 A US3812245 A US 3812245A US 00282100 A US00282100 A US 00282100A US 28210072 A US28210072 A US 28210072A US 3812245 A US3812245 A US 3812245A
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US
United States
Prior art keywords
kiu
streptokinase
99mtc
urokinase
mci
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.)
Expired - Lifetime
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US00282100A
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English (en)
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M Dugan
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Research Corp
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Research Corp
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Publication date
Application filed by Research Corp filed Critical Research Corp
Priority to US00282100A priority Critical patent/US3812245A/en
Priority to FR7320558A priority patent/FR2196788B1/fr
Priority to BE6044231A priority patent/BE802052A/xx
Priority to GB3338073A priority patent/GB1432878A/en
Priority to NL7309907A priority patent/NL7309907A/xx
Priority to DE19732336751 priority patent/DE2336751A1/de
Priority to JP9164173A priority patent/JPS5346915B2/ja
Application granted granted Critical
Publication of US3812245A publication Critical patent/US3812245A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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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
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • 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

  • radio isotopes which fulfill the criteria set forth above are I and '"Tc. Without question “Tc is the most desirable of these radio isotopes. Because of its short physical half life, larger quantities of radioactivity (ie mCi against 300 u Ci for 1) thereby in creasing the photon flux while maintaining a level of radiation which can safely be absorbed by the patient.
  • Eckelman confirms the findings of Richards, Jap. Nucl. Med., 7, 165 (1968) that the removal of stannous hydroxide formed in the course of the reaction is highly advantageous since apparently some radioisotope is occluded upon 'or in the colloidal stannous hydroxide. Eckelman suggests that the optimum conditions of labeling human serum albumin comprise treating the serum albumin with stannous chloride, adjusting the pH to between pH 2 and pH 6, removing any un-bound stannous chloride or stannous hydroxide, and then adding the pertechnetate.
  • Streptokinase and Urokinase covalently labeled with "'Tc covalently labeled with "'Tc.
  • a solution of "'Tc pertechnetate is added to the appropriate enzyme and treated with freshly prepared stannous chloride in dilute hydrochloric acid.
  • the reaction mixture is buffered to a pH greater than 7 allowed to react for a few minutes and the unreacted anions removed, suitably by passage through an anion exchange column.
  • stannous chloride in dilute aqueous hydrochloric acid.
  • stannous chloride in dilute aqueous hydrochloric acid.
  • an alkalizing buffer Any of the commonly used alkaline buffers yielding a pH greater than 7 may be utilized. It is especially preferred however-to utilize buffers having a pH between about 8 and about 12, resulting in a final solution pH between 78.
  • phosphate buffers There may be mentioned phosphate buffers, barbital buffers, and glycine buffers. (Teorell and Steinhagen J. Biol. Chem. 49, 1 83 (1921); Michaelis J. Biol. Chem., 8 7 33 (1930) and idem., Bio chem Z. 234 139 1931; and Sorensen, Biochem Z. 21, 131 (1909) respectively)
  • the mixture is allowed to stand for about 5 minutes and passed through an anion exchange column which will permit the radiolabeled enzyme solution to pass therethrough.
  • Thromboembolists are indicated due to increased radioactivity at the site of the embolists.
  • a radio labeled thrombolytic enzyme selected from the group consisting of "Tc-Streptokinase and '"Tc-Urokinase.
  • Tc-Streptokinase being a compound of claim 1.
  • Tc-Streptokinase being a compound-of claim 2 having an activity of between 0.8 and 2.5 mCi per 10 Kiuof Streptokinase.
  • Tc-Urokinase being a compound of claim 1.
  • a covalent compound of '"Te and Urokinase having an activity of between 0.8 to 2.5 mCi per 10 Kiu of Urokinase.
  • a method of preparing a radio labeled thrombolytic enzyme selected from the group consisting of Streptokinase and Urokinase labeled with *"Tc which comprises the steps of:
  • Step (a) treating from about 5 to about 250 Kiu of said enzyme with from about 15 to about 20 mCi of 99m b. adding to the mixture of Step (a) from about 0.01 to about 4 mg. of freshly prepared stannous chloride and hydrochloric acid,
  • a method according to claim 8 which comprises the sequential steps of:
  • Step (a) treating from about 50 to about 100 Kiu of Streptokinase with from about 15 to about 20 mCi of "'TcO b. adding to the mixture of Step (a) from about 0.1 to about 1 mg. of freshly prepared stannous chloride i fi L LQ-MQQPQH! N YSlI Q acid,
  • Step (b) adding to the acidic solution of Step (b) an alkaline buffer in an amount sufficient to raise the pH to between about 7 and about 8, and
  • a method of detecting thromboembolisms in a vascular system which comprises introducing into said vascular system under examination between about 8 and 350 Kiu of a physiologically acceptable solution of "Tc labeled Streptokinase or Urokinase having a strength of between about 1 and about 20 mCi/Kiu and scanning said vascular system to determine the point of increased gamma radiation.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US00282100A 1972-08-21 1972-08-21 Novel compositions for radiotracer localization of deep vein thrombi Expired - Lifetime US3812245A (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
US00282100A US3812245A (en) 1972-08-21 1972-08-21 Novel compositions for radiotracer localization of deep vein thrombi
FR7320558A FR2196788B1 (enrdf_load_html_response) 1972-08-21 1973-06-06
BE6044231A BE802052A (fr) 1972-08-21 1973-07-06 Enzymes thrombolytiques a marquage isotopique
GB3338073A GB1432878A (en) 1972-08-21 1973-07-12 Compositions for radiotracer localization
NL7309907A NL7309907A (enrdf_load_html_response) 1972-08-21 1973-07-17
DE19732336751 DE2336751A1 (de) 1972-08-21 1973-07-19 Neue zusammensetzungen fuer die lokalisation von tiefliegenden gefaessthromben mit radioaktivem spuerstoff
JP9164173A JPS5346915B2 (enrdf_load_html_response) 1972-08-21 1973-08-15

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US00282100A US3812245A (en) 1972-08-21 1972-08-21 Novel compositions for radiotracer localization of deep vein thrombi

Publications (1)

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US3812245A true US3812245A (en) 1974-05-21

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US00282100A Expired - Lifetime US3812245A (en) 1972-08-21 1972-08-21 Novel compositions for radiotracer localization of deep vein thrombi

Country Status (7)

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US (1) US3812245A (enrdf_load_html_response)
JP (1) JPS5346915B2 (enrdf_load_html_response)
BE (1) BE802052A (enrdf_load_html_response)
DE (1) DE2336751A1 (enrdf_load_html_response)
FR (1) FR2196788B1 (enrdf_load_html_response)
GB (1) GB1432878A (enrdf_load_html_response)
NL (1) NL7309907A (enrdf_load_html_response)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3927193A (en) * 1973-05-18 1975-12-16 Hoffmann La Roche Localization of tumors by radiolabelled antibodies
US4036945A (en) * 1976-05-03 1977-07-19 The Massachusetts General Hospital Composition and method for determining the size and location of myocardial infarcts
US4224303A (en) * 1978-07-21 1980-09-23 A. C. Smith Signalling particles for introduction into blood flowing through a vessel of interest
WO1981001417A1 (en) * 1979-11-13 1981-05-28 S Husain Isolation of plasminogen activators useful as therapeutic and diagnostic agents
US4293537A (en) * 1978-09-05 1981-10-06 Wong Dennis W Novel chemical method of labeling proteins with 99m Tc-Technetium at physiological condition
US4385046A (en) * 1980-12-15 1983-05-24 Minnesota Mining And Manufacturing Company Diagnostic radio-labeled polysaccharide derivatives
US4416865A (en) * 1973-02-20 1983-11-22 Research Corporation Radiopharmaceuticals for localization of thromboembolic disease
US4453075A (en) * 1979-10-17 1984-06-05 Mattsson Soeren Method for localizing a region in the human body, in particular venous thrombi, by the uptake of a radioactive substance, particularly 125 I-
USRE32271E (en) * 1979-11-13 1986-10-28 Isolation of plasminogen activators useful as therapeutic and diagnostic agents

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS54165220U (enrdf_load_html_response) * 1978-05-12 1979-11-20
JPS5597349A (en) * 1978-12-28 1980-07-24 Showa Seitai Mfg Bag with pleat
JPS5598747U (enrdf_load_html_response) * 1978-12-28 1980-07-09
EP2199731B1 (de) 2008-12-18 2015-02-11 Rheinmetall Waffe Munition ARGES GmbH Haftladung

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4416865A (en) * 1973-02-20 1983-11-22 Research Corporation Radiopharmaceuticals for localization of thromboembolic disease
US3927193A (en) * 1973-05-18 1975-12-16 Hoffmann La Roche Localization of tumors by radiolabelled antibodies
US4036945A (en) * 1976-05-03 1977-07-19 The Massachusetts General Hospital Composition and method for determining the size and location of myocardial infarcts
US4224303A (en) * 1978-07-21 1980-09-23 A. C. Smith Signalling particles for introduction into blood flowing through a vessel of interest
US4293537A (en) * 1978-09-05 1981-10-06 Wong Dennis W Novel chemical method of labeling proteins with 99m Tc-Technetium at physiological condition
US4453075A (en) * 1979-10-17 1984-06-05 Mattsson Soeren Method for localizing a region in the human body, in particular venous thrombi, by the uptake of a radioactive substance, particularly 125 I-
WO1981001417A1 (en) * 1979-11-13 1981-05-28 S Husain Isolation of plasminogen activators useful as therapeutic and diagnostic agents
USRE32271E (en) * 1979-11-13 1986-10-28 Isolation of plasminogen activators useful as therapeutic and diagnostic agents
US4385046A (en) * 1980-12-15 1983-05-24 Minnesota Mining And Manufacturing Company Diagnostic radio-labeled polysaccharide derivatives

Also Published As

Publication number Publication date
JPS5346915B2 (enrdf_load_html_response) 1978-12-16
NL7309907A (enrdf_load_html_response) 1974-02-25
GB1432878A (en) 1976-04-22
DE2336751A1 (de) 1974-02-28
FR2196788A1 (enrdf_load_html_response) 1974-03-22
BE802052A (fr) 1973-11-05
FR2196788B1 (enrdf_load_html_response) 1978-07-28
JPS4965890A (enrdf_load_html_response) 1974-06-26

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