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1. WO2004054623 - PROCEDE D'IMAGERIE PAR RESONANCE MAGNETIQUE ET COMPOSES DESTINES A ETRE UTILISES DANS LE PROCEDE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]
Claims:

1. Method of MR imaging comprising
a) administering a contrast agent comprising at least one complex comprising a paramagnetic metal ion and a complexing moiety to a human or non-human animal body wherein said complex has a thermodynamic formation constant between 103 and 1016;
b) exposing said body to a regime of physical and/or pharmacological stress before or simultaneously to the contrast agent administration;
c) collecting MR imaging data and;
d) optionally providing MR images of an area of interest.

2. Method according to claim 1, wherein the contrast agent comprises a mixture of complexes.

3. Method according to claim 1 and 2, wherein the complexing moiety is a low molecular weight hydrophilic complexing moiety.

4. Method according to claims 1 to 3, wherein the complexing moiety is a complexing moiety selected from the group consisting of N,N'-bis-(pyridoxal-5- phosphate)ethylenediamine-N,N'-diacetic acid (DPDP), N,N'-bis-pyridoxal- ethylene-diamine-N,N'-diacetic acid (PLED), diethylenetraminepentaacetic acid-bismethylamide (DTPABMA), ethylenediaminetetraacetic acid- bismethylamide (EDTABMA), polyphosphates, triphosphate (P3Oιo5~; TPP) and 1 ,7-dicarboxy-2,6-bis(carboxymethyl)-4-hydroxy-2,6-diaza)-heptane (HPTA).

5. Method according to claims 1 to 4, wherein the complexing moiety is a complexing moiety selected from the group consisting of DPDP, TPP and HPTA.

6. Method according to claims 1 to 5, wherein the paramagnetic metal ion is a manganese ion, preferably Mn 2+

PN02113-PCT/FI/16.12.03

7. Method according to claims 1 to 6, wherein the thermodynamic formation constant k is between 105 and 1010, preferably between 107 and 1095.

8. Method according to claims 1 to 7, wherein the paramagnetic metal ion is Mn2+ and said complex shows a dissociation of greater than 50% and a half-life of less than 1 min under physiological conditions.

9. Method according to claims 1 to 8, wherein the paramagnetic metal ion is Mn2+ and the contrast agent comprises 0 to 2 mol Ca2+ per mol Mn2+, preferably 0.1 to 1.75 mol Ca + per mol Mn2+, more preferably 0.5 to 1 mol Ca2+ per mol Mn2+.

10. Method according to claims 1 to 9, wherein the stress is a physical stress.

11. Method according to claims 1 to 10, wherein the contrast agent is administered at peak stress.

12. Method according to claims 1 to 11, wherein MR images of an area of interest, preferably the myocardium, are provided.

13. Method according to claims 1 to 12, wherein the method is used to identify diseased areas comprising areas suffering from myocardial ischemia.

14. Compound of the formula (I)


where m, n and o are positive integers from 1 to 10 and Z is hydrogen or a pharmaceutical acceptable counterion for use in a MR contrast agent.

PN02113-PCT/FI/16.12.03

15. Use of compounds of the formula (I)

Mnm(P3O105")nZo (I)
wherein m, n and o are positive integers from 1 to 10 and Z is hydrogen or a pharmaceutical acceptable counterion for the manufacture of a contrast agent for use in MR imaging.

16. Use of compounds of the formula (II)

MnmHPTA Z0 (II)

where m is 1 or 2, o is 0 to 2 , Z is hydrogen or a pharmaceutical acceptable counterion for the manufacture of a contrast agent for use in the detection of myocardial ischemia.

17. Use according to claim where Mn is Mn2+, m is 1 or 2, o is 0 or 2 and Z is hydrogen, sodium or calcium.

18. Use of a mixture comprising a complex having a thermodynamic formation constant between 103 and 1016 which comprises Mn2+ and a complexing moiety, wherein said complex shows a dissociation of greater than 50% and a half-life of less than 1 min under physiologic conditions and 0.1 to 2 mol Ca2+ per mol Mn2+ for the manufacture of a contrast agent for use in MR imaging of the myocardium, preferably for use in the MR imaging detection of myocardial ischemia and infarction.

19. Use according to claim 18, wherein the mixture comprises 0.5 to 1 mol Ca2+ per mol Mn2+.

20. Use according to claims 18 and 19, wherein the complexing moiety is HPTA.

PN02113-PCT/FI/16.12.03