Diamide-DTPA-paramagnetic contrast agents for MR imaging

Claim 2

A chemically stable physiologically tolerable contrast agent in a solid state, for use in vivo solution during diagnostic magnetic resonance (MR) imaging, to enhance the MR image the region of interest of a subject within the MR scanning magnetic field, comprising: a composition of matter of the form: A-DTPA-PM(+Z), where: A-DTPA is an ethylene triamine pentaacetic acid chelator in which at least one of the five acetic acid groups has become a functional amide group A of the form: A=--CONH--(CH 2 ) n-1 -CH 3 , wherein "n" is an integer up to 16 indicating the number of Carbon atoms in the Carbon-Hydrogen portion of the amide group A, for functionally cooperating with the in vivo environment; and PM(+Z) is a paramagnetic metal ion having an atomic charge of Z, securely chelated at a plurality of coordination points into the A-DTPA chelator to chemically isolate the PM(+Z) ion from the in vivo environment, for locally affecting the magnetic field of the MR system; whereby the contrast agent causes a reduction in the T1 relaxation time near the region of interest within the subject.

Claim 3

The contrast agent of claim 1, wherein the composition of matter is a diamide of the form: 2A-DTPA-PM(+Z), where: 2A-DTPA-PM(+Z) is ethylene triamine pentaacetic acid chelator in which two of the five acetic acid groups have been become a pair of functional amide groups A of the form: A=--CONH--(CH 2 ) n-1 --CH 3 , wherein n is an integer up to 16, indicating the number of Carbon atoms in the Carbon-Hydrogen portion of each amide group.

Claim 4

The contrast agent of claim 2, wherein Z=+3 and 2A-DTPA-PM(+3) is a molecule having a zero net charge.

Claim 5

The contrast agent of claim 2, wherein Z=+2 and the composition of matter has the form: 2A-IN-DTPA-PM(+2), where: IN is an inert cation of charge +1; and 2A-IN-DTPA-PM(+2) is a molecule having a zero net charge.

Claim 6

The contrast agent of claim 1, wherein the paramagnetic metal ion PM(+Z) within the composition of matter is at least one element selected from the group consisting of: ______________________________________ Ions of Transition Elements ______________________________________ Cr(III) Co(II) Mn(II) Ni(II) Fe(III) Cu(III) Fe(II) Cu(II) ______________________________________ ______________________________________ Ions of Lanthanide Elements ______________________________________ La(III) Gd(III) Ce(III) Tb(III) Pr(III) Dy(III) Nd(III) Ho(III) Pm(III) Er(III) Sm(III) Tm(III) Eu(III) Yb(III) Lu(III). ______________________________________

Claim 7

The contrast agent of claim 1, wherein the paramagnetic metal ion PM(+Z) within the composition of matter is at least one element selected from the group consisting of: ______________________________________ Cr(III) Co(II) Mn(II) Ni(II) Fe(III) Cu(III) Fe(II) Cu(II). Gd(II) ______________________________________

Claim 8

A chemically stable physiologically tolerable contrast agent in a pharmacological state, for in vivo use during diagnostic magnetic resonance (MR) imaging, to enhance the MR image of a subject within the MR scanning magnetic field, comprising: a paramagnetic metal ion PM(+Z) having an atomic charge of Z for locally affecting the MR scanning magnetic field within the subject to reduce the T1 relaxation time thereof; a triamine chelator DTPA' securely polar bonded around the PM(+Z) ion at a plurality of coordination points to provide a DTPA'-PM, and having the form: ##STR5## for chemically isolating the PM(+Z) ion from the in vivo environment; functional group means formed by an amide compound of the form CONH 2 --(CH 2 ) n-1 --CH 3 , wherein "n" is an integer indicating the number of Carbon atoms in the Carbon-Hydrogen portion of the amide compound, for functionally cooperating with the in vivo environment, covalently bonded to the DTPA'-PM chelator forming an Amide-DTPA'-PM contrast agent; and a pharmaceutically acceptable vehicle means for dispersing the Amide-DTPA'-PM contrast agent.

Claim 9

A chemically stable physiologically tolerable contrast agent in a pharmacological state, for in vivo use during diagnostic magnetic resonance (MR) imaging, to enhance the MR image of a subject within the MR scanning magnetic field, comprising: a paramagnetic metal ion PM(+Z) having an atomic charge of Z for locally affecting the MR scanning magnetic field within the subject to reduce the T1 relaxation time thereof; a triamine chelator DTPA' securely polar bonded around the PM(+Z) ion at a plurality of coordination points to provide a DTPA'-PM, and having the form: ##STR5## for chemically isolating the PM(+Z) ion from the in vivo environment; functional group means formed by an amide compound of the form CONH 2 --(CH 2 ) n-1 --CH 3 , wherein "n" is an integer indicating the number of Carbon atoms in the Carbon-Hydrogen portion of the amide compound, for functionally cooperating with the in vivo environment, covalently bonded to the DTPA'-PM chelator forming an Amide-DTPA'-PM contrast agent; and a pharmaceutically acceptable vehicle means for dispersing the Amide-DTPA'-PM contrast agent.

Claim 10

The contrast agent of claim 7, wherein the functional group means comprises: a first amide group having n1 Carbon atoms in Carbon-Hydrogen portion, and covalently bonded to the DTPA'-PM chelator; and a second amide group having n2 Carbon atoms in Carbon-Hydrogen portion, and covalently bonded to the DTPA'-PM chelator; to form a Diamide-DTPA'-PM.

Claim 11

The contrast agent of claim 8, wherein n1 and n2 may by any whole integer from 0 to 16.

Claim 12

The contrast agent of claim 9, wherein the Diamide-DTPA'-PM is a homo-diamide in which n1=n2.

Claim 13

The contrast agent of claim 9, wherein the Diamide-DTPA'-PM is a hetero-diamide in which n1 is larger than n2.

Claim 14

The contrast agent of claim 7, wherein Z=+3 and the Amide-DTPA'-PM has a zero net charge.

Claim 15

The contrast agent of claim 7, wherein Z=+2 and the further comprises an inert cation IN having an atomic charge of +1 forming Amide-IN(+1)-DTPA'-PM(+2) with a zero net charge.

Claim 16

The contrast agent of claim 7, wherein the vehicle means is a water solution.

Claim 17

The contrast agent of claim 14, further comprising water of hydration associated with the Carbon-Hydrogen portion to the amide compound.

Claim 18

The contrast agent of claim 7, wherein the paramagnetic metal ion (PM(+Z) is at least one element selected from the group consisting of: ______________________________________ Ions of Transition Elements ______________________________________ Cr(III) Co(II) Mn(II) Ni(II) Fe(III) Cu(III) Fe(II) Cu(II) ______________________________________ ______________________________________ Ions of Lanthanide Elements ______________________________________ La(III) Gd(III) Ce(III) Tb(III) Pr(III) Dy(III) Nd(III) Ho(III) Pm(III) Er(III) Sm(III) Tm(III) Eu(III) Yb(III) Lu(III). ______________________________________

Claim 19

The contrast agent of claim 7, wherein the paramagnetic metal ion PM(+Z) is at least one element selected from the group consisting of: ______________________________________ Cr(III) Co(II) Mn(II) Ni(II) Fe(III) Cu(III) Fe(II) Cu(II). Gd(II) ______________________________________

Claim 20

The contrast agent of claim 7, wherein the paramagnetic metal ion PM(+Z) is Fe(III).

Claim 21

The contrast agent of claim 7, wherein the paramagnetic metal ion PM(+Z) is Mn(II).

Claim 22

The contrast agent of claim 7, wherein the paramagnetic metal ion PM(+Z) is Co(II).

Claim 23

The contrast agent of claim 7, wherein the paramagnetic metal ion PM(+Z) is Gd(III).

Claim 26

The method of imaging a subject as specified in claim 22, wherein the contrast agent is introduced by intravenous injection.

Claim 27

The method of imaging a subject as specified in claim 22, further comprising the initial step of dispersing the 2A-DTPA-PM contrast agent into a suitable carrier vehicle.

Claim 28

The method of imaging a subject as specified in claim 22, further comprising: the initial step of providing data from a prior MR imaging: and the final step of subtraction comparing the prior MR image with the current MR image.

Claim 29

The method of imaging a subject as specified in claim 22, wherein the region of interest is the gall bladder and the colon.

Claim 30

The method of imaging a subject as specified in claim 26, wherein the resulting image is a perspective image of the surface of the colon.