US3812245A - Novel compositions for radiotracer localization of deep vein thrombi - Google Patents
Novel compositions for radiotracer localization of deep vein thrombi Download PDFInfo
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- 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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- Prior art keywords
- kiu
- streptokinase
- 99mtc
- urokinase
- mci
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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
- A61K51/08—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)
- Investigating Or Analysing Biological Materials (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
There are provided radiolabeled enzymes, namely 99mTcStreptokinase and Urokinase which have thrombolytic activity and in view of their propensity to accumulate at the location of the thrombi provide an effecient means of locating said thrombi.
Description
United States Patent 9] Dugan NOVEL COMPOSITIONS FOR RADIOTRACER LOCALIZATION OF DEEP VEIN THROMBI [75] Inventor: Mary Ann Dugan, Philadephia, Pa.
[73] Assignee: Research Corporation, New York,
22 Filed: Aug. 21,1972 21 Appl. No.: 282,100
[52] U.S. Cl 424/1, 250/7l.5 S [51] Int. Cl. A6lk 27/04, GOlt 1/20 [58] Field of Search 424/1, 94; 250/106 T, 71.5 S
[56] References Cited OTHER PUBLICATIONS Nuclear Science Abstracts, Vol. 21, No. 20, Oct.- 31,
[111 3,812,245 [451 May 21,1974
1967, p. 3834, Item No. 36,623.
Abstracted from Vestn. Akad Med. Nauk SSSR 22: N0. 4.
Primary Examiner-Benjamin R. Padgett Attorney, Agent, or Firm-Omril M. Behr, Esq.
[5 7] ABSTRACT 11 Claims, No Drawings FIELD OF THE INVENTION Radiolabeled thrombolytic enzymes.
DESCRIPTION OF THE PRIOR ART The location of thromboembolisms in the vascular system has long been considered a problem to which rapid and accurate solutions are desirable. One of the techniques which has been employed has been injection of radiotracer materials into the blood stream generally (Griep, Radiology, 97, 311,1970). In this work radioisotopes were tracked throughout the system where the embolism is believed to reside. Since the location of the venous system in the human body is fairly well known, the blockage of flow of radiotracer indicates the location of the occlusion. This method however does not permit the rapid and accurate localization of the embolisms. 1 labeled fibrinog'en has been used in the detection of thrombi (Flanc, et al., Brit. J. Surg. 55,742, 1968 and OBrien, Lancet, 396, 1970). Unfortunately, fibrinogen cannot be incorporated into or attracted to an existing thrombus, thus limiting the concentration of detectable radioactivity. It would therefore be desirable to label a physiologically acceptable material which is attracted to and incorporated in a thrombo embolism giving rise to a high concentration of radioactivity at that point. Concomitant therewith it would be necessary to utilize a labeling isotope of high photon flux within acceptable patient radiation adsorped dose limits, which had a half-life sufficient to permit circulation throughout the vascular system.
Among the 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.
Much work has been done recently on the incorporation of "Tc into human serum albumin which is a protein. The reported work in this area indicates that the reaction conditions for labeling human serum albumin with '"Tc are extremely sensitive. Care must be taken v on the one hand to avoid conditions which lead to the denaturation of the protein and on the other hand which lead to the absorption of a substantial portion of the radioisotope on side-products of the reaction, such as colloidal stannous hydroxide. The problems in this work are mentioned in Eckelman, et al., Journal of Nuclear Medicine, 12, 707, 1971; Lin, et al., J. Nucl.
Med., 12, 204, 1971; all of these workers have shown that the proportion of stannous chloride as a reducing agent is critical to the success of coupling the radiosotope to the protein.
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.
SUMMARY OF THE INVENTION The invention described herein was made in the course of work under a grant or award from theDepartment of Health, Education and Welfare.
There is provided Streptokinase and Urokinase covalently labeled with "'Tc. In the process of preparing these labeled enzymes, 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.
DESCRIPTION OF THE PREFERRED EMBODIMENTS In the process of the present invention there is utilized as a starting material between 5,000 and 250,000 international units (hereinafter 5 to 250 Kiu) of Streptokinase or Urokinase. Streptokinase is generally preferred because of its greater availability. To this starting material is added ""lechnetium pertechnetate. There is added a quantity corresponding to initial radioactivity of from about 15 to about 20 mCi. The degree of dilution of the pertechnetate is not critical, however it is generally preferred to utilize an aqueous solution containing from about 5 to about 10 mCi per ml.
To this mixture of enzyme and pertechnetate is added freshly prepared stannous chloride in dilute aqueous hydrochloric acid. There may be utilized between 0.1 to about 4mg. of stannous chloride in 1 ml. of between 0.1N and 2N l-lCl. It is generally preferred however to utilize from about 0.1 to about 0.5 mg. of stannous chloride in from about 0.1 to about 0.5N HCl. To this mixture is added 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. 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.
While applicants do not base their invention thereon, there is reason to beleive that one or more "'Technetium atoms are incorporated into the protein chain of the enzyme, probably by displacing the cyclic hydroxyl moiety or a ring hydrogen proximate thereto in the tyrosive segment of the protein.
In utilizing the novel Tc labeled enzymes of the presentinvention there are injected into the venous system between about 1 to about 10 ml. of solution having a radioactivity of between 1 and 20 mCi and bioactivity of between and 350 Kiu.
Whole body scans are then taken at various time interval e.g. /2 to 4 hrs. past administration, using suitable detectors e.g. rectelinear scannings techniques or Anger Scintillation Camera studies. Thromboembolists are are indicated due to increased radioactivity at the site of the embolists.
EXAMPLE 1 Tc STREPTOKINASE To a vial containing 100Kiu Streptokinase is added 2 ml. of an aqueous solution of Technetium pertechnetate having a flux of 15 to 20 mCi. To this mixture is added 1 ml. of freshly prepared stannous chloride in hydrochloric acid (100 mg./liter, 0.2N), followed by 1 ml. of phosphate buffer (pH 12).
h m x ur s al d to .standmfo 5 ninu esand passed through an anion exchange column (Dowex 1-X8, 2 cm X mm. diameter column, 2 ml.). The coupled '"Tc-Streptokinase solution will pass through the column which will retain unreacted cationic material.
ln accordance with the foregoing procedure but using Urokinase instead of Streptokinase there is obtained Tc-Urokinase.
I claim:
1. A radio labeled thrombolytic enzyme selected from the group consisting of "Tc-Streptokinase and '"Tc-Urokinase.
2. Tc-Streptokinase, being a compound of claim 1.
3. "Tc-Streptokinase, being a compound-of claim 2 having an activity of between 0.8 and 2.5 mCi per 10 Kiuof Streptokinase.
4. A covalent compound of "'Te and Streptokinase having an activity of between 0.8 to 2.5 mCi per 10 Kiu of Streptokinase.
5. Tc-Urokinase, being a compound of claim 1.
6. ""Ic-Urokinase, being a compound of claim 5 having an activity of between 0.8 and 25 mCi per 10 Kiu of Urokinase.
7. A covalent compound of '"Te and Urokinase having an activity of between 0.8 to 2.5 mCi per 10 Kiu of Urokinase.
8. 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:
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,
c. raising the pH to between about 7 and 8 and,
d. removing the unreacted pertechnetate from the mixture.
9. A method according to claim 8 which comprises the sequential steps of:
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,
c. 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
d. passing the mixture of Step (c) exchange column.
10. 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.
11. A method according to claim 10 wherein there is injected between about 8 and 350 Kiu of a physiologically acceptable solution of '"Te labeled Streptokinase having a strength of between about 1 and 20 mCi/- Kiu.
through an anion I Notice of Adverse Decision in Interference In Interference/No. 99,133, involving Patent No. 3,812,245, M. A. Dugan, NOVEL COMPOSITIONS FOR RADIOTRACER LOCALIZATION OF DEEP VEIN THROMBI, final judgment adverse to the patentee was rendered Oct. 29, 1981, as to claims 1, 5 & 10.
[Ofiicial Gazette April 6, 1982.]
Notice of Adverse Decision in Interference 1 In Interference N0. 99,133, involving Patent No. 3,812,245, M. A. Dugan, NOVEL COMPOSITIONS FOR RADIOTRACER LOCALIZATION OF DEEP VEIN THROMBI, final judgment adverse to the patentee was rendered Oct. 29, 1981, as to claims 1, 5 & 10.
[Official Gazette April 6, 1982.]
Claims (10)
- 2. 99mTc-Streptokinase, being a compound of claim 1.
- 3. 99mTc-Streptokinase, being a compound of claim 2 having an activity of between 0.8 and 2.5 mCi per 10 Kiu of Streptokinase.
- 4. A covalent compound of 99mTc and Streptokinase having an activity of between 0.8 to 2.5 mCi per 10 Kiu of Streptokinase.
- 5. 99mTc-Urokinase, being a compound of claim 1.
- 6. 99mTc-Urokinase, being a compound of claim 5 having an activity of between 0.8 and 2.5 mCi per 10 Kiu of Urokinase.
- 7. A covalent compound of 99mTc and Urokinase having an activity of between 0.8 to 2.5 mCi per 10 Kiu of Urokinase.
- 8. A method of preparing a radio labeled thrombolytic enzyme selected from the group consisting of Streptokinase and Urokinase labeled with 99mTc which comprises the steps of: a. treating from about 5 to about 250 Kiu of said enzyme with from about 15 to about 20 mCi of 99mTcO4, b. adding to the mixture of Step (a) from about 0.01 to about 4 mg. of freshly prepared stannous chloride and hydrochloric acid, c. raising the pH to between about 7 and 8 and, d. removing the unreacted pertechnetate from the mixture.
- 9. A method according to claim 8 which comprises the sequential steps of: a. treating from about 50 to about 100 Kiu of Streptokinase with from about 15 to about 20 mCi of 99mTcO4, b. adding to the mixture of Step (a) from about 0.1 to about 1 mg. of freshly prepared stannous chloride in from about 0.1 to about 1N hydrochloric acid, c. 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 d. passing the mixture of Step (c) through an anion exchange column.
- 10. 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 99mTc 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.
- 11. A method according to claim 10 wherein there is injected between about 8 and 350 Kiu of a physiologically acceptable solution of 99mTc labeled Streptokinase having a strength of between about 1 and 20 mCi/Kiu.
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 (en) | 1972-08-21 | 1973-06-06 | |
BE6044231A BE802052A (en) | 1972-08-21 | 1973-07-06 | ISOTOPICALLY LABELED THROMBOLYTIC ENZYMES |
GB3338073A GB1432878A (en) | 1972-08-21 | 1973-07-12 | Compositions for radiotracer localization |
NL7309907A NL7309907A (en) | 1972-08-21 | 1973-07-17 | |
DE19732336751 DE2336751A1 (en) | 1972-08-21 | 1973-07-19 | NEW COMPOSITIONS FOR THE LOCALIZATION OF LOW-FLYING HAZARDOUS THROMBES WITH RADIOACTIVE PETROL |
JP9164173A JPS5346915B2 (en) | 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)
Publication Number | Publication Date |
---|---|
US3812245A true US3812245A (en) | 1974-05-21 |
Family
ID=23080113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US00282100A Expired - Lifetime US3812245A (en) | 1972-08-21 | 1972-08-21 | Novel compositions for radiotracer localization of deep vein thrombi |
Country Status (7)
Country | Link |
---|---|
US (1) | US3812245A (en) |
JP (1) | JPS5346915B2 (en) |
BE (1) | BE802052A (en) |
DE (1) | DE2336751A1 (en) |
FR (1) | FR2196788B1 (en) |
GB (1) | GB1432878A (en) |
NL (1) | NL7309907A (en) |
Cited By (9)
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 (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54165220U (en) * | 1978-05-12 | 1979-11-20 | ||
JPS5760994Y2 (en) * | 1978-12-19 | 1982-12-25 | ||
JPS5597349A (en) * | 1978-12-28 | 1980-07-24 | Showa Seitai Mfg | Bag with pleat |
JPS5598747U (en) * | 1978-12-28 | 1980-07-09 | ||
EP2199731B1 (en) | 2008-12-18 | 2015-02-11 | Rheinmetall Waffe Munition ARGES GmbH | Adhesive charge |
-
1972
- 1972-08-21 US US00282100A patent/US3812245A/en not_active Expired - Lifetime
-
1973
- 1973-06-06 FR FR7320558A patent/FR2196788B1/fr not_active Expired
- 1973-07-06 BE BE6044231A patent/BE802052A/en unknown
- 1973-07-12 GB GB3338073A patent/GB1432878A/en not_active Expired
- 1973-07-17 NL NL7309907A patent/NL7309907A/xx unknown
- 1973-07-19 DE DE19732336751 patent/DE2336751A1/en active Pending
- 1973-08-15 JP JP9164173A patent/JPS5346915B2/ja not_active Expired
Cited By (9)
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 |
---|---|
NL7309907A (en) | 1974-02-25 |
BE802052A (en) | 1973-11-05 |
FR2196788B1 (en) | 1978-07-28 |
DE2336751A1 (en) | 1974-02-28 |
FR2196788A1 (en) | 1974-03-22 |
JPS5346915B2 (en) | 1978-12-16 |
JPS4965890A (en) | 1974-06-26 |
GB1432878A (en) | 1976-04-22 |
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