Patent US4880008A successfully refreshed from Google Patents.
US4880008A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Vivo enhancement of NMR relaxivity
Assignee: General Hospital Corp
•
Filing: 1986-05-07
•
Granted: 1989-11-14
•
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 21:38
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.
References Cited (Backward Citations)
DE2606721A1
Cited
AU8633082A
Cited
DE3129906A1
Cited
EP0169299A2
Cited
US4647447A
Cited
US4472509A
Cited
EP0133603A1
Cited
WO1985002272A1
Cited
US4615879A
Cited
WO1985005554A1
Cited
WO1986001410A1
Cited
WO1986002352A1
Cited
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 |