US4880008A
Expired / Lapsed
US
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Vivo enhancement of NMR relaxivity
Assignee: General Hospital Corp
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Filing: 1986-05-07
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Granted: 1989-11-14
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Expires: 2006-05-07
Abstract
Abstract A method of decreasing the NMR relaxation times (T1 or T2) of water protons in contact with a biological tissue, the method involving administering to a human patient an NMR contrast agent comprising a paramagnetic ion complexed with a chelating substance, the contrast agent being characterized in that it is capable of binding non-covalently and non-immunologically to a component of the tissue, and as a result of such binding is capable of enhancing relaxivity of the water protons by a factor of at least 2, compared to the relaxivity induced by the paramagnetic substance alone free in solution, and subjecting the patient to NMR imaging.
Inventors
- 👤 Randall B. Lauffer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:06
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
186 words
A method of decreasing the NMR relaxation times (T 1 or T 2 ) of water protons in contact with a biological tissue, said method comprising: providing an NMR contrast agent which does not include an antibody and which comprises a paramagnetic ion selected from the group of ions consisting of gadolinium (III), iron (III), manganese (II and III), chromium (III), copper (II), dysprosium (III), terbium (III); holmium (III), erbrium (III) and europium (III), complexed with a chelating substance having at least one aryl ring which may be substituted in one or more positions with members of the group consisting of the halogens and the C 1 -C 10 alkyl groups, said contrast agent being characterized in that it is capable of binding non-covalently to ligandin, or Protein A, or HSA of said tissue and as a result of such binding is capable of enhancing relaxivity of said water protons by a factor of at least 2, compared to the relaxivity induced by said paramagnetic substance alone free in solution, administering said NMR contrast agent to a human patient, and subjecting said patient to NMR imaging.
Claim 2
Independent Claim
186 words
A method of decreasing the NMR relaxation times (T 1 or T 2 ) of water protons in contact with a biological tissue, said method comprising: providing an NMR contrast agent which does not include an antibody and which comprises a paramagnetic ion selected from the group of ions consisting of gadolinium (III), iron (III), manganese (II and III), chromium (III), copper (II), dysprosium (III), terbium (III); holmium (III), erbrium (III) and europium (III), complexed with a chelating substance having at least one aryl ring which may be substituted in one or more positions with members of the group consisting of the halogens and the C 1 -C 10 alkyl groups, said contrast agent being characterized in that it is capable of binding non-covalently to ligandin, or Protein A, or HSA of said tissue and as a result of such binding is capable of enhancing relaxivity of said water protons by a factor of at least 2, compared to the relaxivity induced by said paramagnetic substance alone free in solution, administering said NMR contrast agent to a human patient, and subjecting said patient to NMR imaging.
Claim 3
Dependent Claim
57 words
The method of claim 1 wherein the chelating substance is selected from the group consisting of ethylenebis-(2-hydroxyphenylglycine) and its derivatives having the structure: ##STR18## wherein each n and m, independently, is an integer between 0 and 4 inclusive, and each R 1 and R 2 , independently, is Cl, Br, I, CH 3 , t-Bu, or sec-Bu.
Claim 4
Dependent Claim
59 words
The method of claim 1 wherein the chelating substance is selected from the group consisting of benzodiethylenetriamine-pentaacetic acid and its derivatives having the structures: ##STR19## wherein n is an integer between 0 and 4 inclusive, and each R 1 independently, can be Cl,Br,I,CH 3 , t-Bu or sec-Bu and R 2 , independently, can be benzo, benzyl or phenyl.
Claim 5
Dependent Claim
59 words
The method of claim 1 wherein the chelating substance is selected from the group consisting of bis-2(hydroxybenzyl)-ethylene-diaminediacetic acid and its derivatives having the structure: ##STR20## wherein each n and m, independently, is an integer between 0 and 4 inclusive, and each R 1 and R 2 , independently, can be Cl, Br, I, Ch 3 , t-Bu, or sec-Bu.
Claim 6
Dependent Claim
133 words
The method of claim 1 wherein the chelating substance is selected from the group consisting of mono- and multi-macrocyclic compounds having between 3 and 6 carbon atoms and at least two hetero atoms from the group of O and N, wherein the mono-macrocyclic compounds have the general structure: ##STR21## wherein: A can be ##STR22## X, independently, is an integer between 0 and 1, inclusive, and R 5 ,R 6 ,R 7 , and R 8 , independently can be H or methyl and R 1 ,R 2 ,R 3 and R 4 , independently, can be ethyl, propyl, butyl, pentyl or ##STR23## provided that when A is ##STR24## at least one R must be ##STR25## and wherein said aryl groups may be substituted with halogen atoms or C 1 -C 4 alkyl groups.
Claim 7
Dependent Claim
50 words
The method of claim 1 wherein the chelating substance is selected from the group consisting of derivatives of diethylenetriamine-penta acetic acid having the structure ##STR26## wherein R 1 , R 2 , R 3 ,R 4 and R 5 independently can be a C 6-10 aryl or C 1-5 aliphatic.
Claim 8
Dependent Claim
39 words
The method of claim 1 wherein the chelating substance is from the group of substances consisting of derivatives of 1,3 - propylenediaminetetraacetic acid having the structure: ##STR27## wherein R 1 can be C 6-10 aryl or C 1-5 aliphatic.
Claim 9
Dependent Claim
54 words
The method of claim 1 wherein the chelating substance is from the group of substances consisting of derivatives of triethylenetetraaminehexacetic acid having the structure: ##STR28## wherein R 2 , R 3 , R 4 , R 5 , R 6 and R 7 , independently can be C 6-10 aryl or C 1-5 aliphatic.
Claim 10
Dependent Claim
52 words
The method of claim 1 wherein the chelating substance is from the group of substances consisting of derivatives of 1,5,10-N,N',N"-tris(2,3-dihydroxybenzoyl)-tricatecholate having the structure: ##STR29## wherein each R 4 , R 5 and R 6 , independently, can be CO 2 H, SO 3 H, H, Cl, Br, I, or C 1-5 alkyl.
Claim 11
Dependent Claim
54 words
The method of claim 1 wherein the chelating substance is from the group of substances consisting of: derivatives of 1,3,5-N,N',N"-tris(2, 3-dihydroxybenzoyl)-aminomethylbenzene having the structure: ##STR30## wherein each R 4 , R 5 , and R 6 , independently, can be CO 2 H, SO 2 H, H, Cl, Br, I, or C 1-5 alkyl.
Claim 12
Dependent Claim
49 words
The method of claim 1 wherein the chelating substance is a derivative of 1, 4, 7, 10-tetraazocyclotetradecane-1,4,7,10-tetraacetic acid containing hydrophobic substituents attached to one or more of carbon atoms 1-8, said substituents being C 6-10 aryl groups e.g., phenyl or benzyl, or C 1-5 aliphatic, e.g., methyl or ethyl.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-11-13 | 1993-05-15 | 1993-11-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-13 | 1997-05-15 | 1997-11-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-11-13 | 2001-05-15 | 2001-11-14 | $7700.00 | Window Closed / Lapsed |