	US 7,524,483 B2
	Responsive paramagnetic MRI contrast agents
Silvio Aime, Carignano (Italy); Daniela Delli Castelli, Bibiana (Italy); Franco Fedeli, Vimodrone (Italy); and Enzo Terreno, Turin (Italy)
Assigned to Bracco Imaging S.p.A., Milan (Italy)
Appl. No. 10/502,701 PCT Filed Jan. 27, 2003, PCT No. PCT/EP03/00796 § 371(c)(1), (2), (4) Date Jul. 27, 2004, PCT Pub. No. WO03/063912, PCT Pub. Date Aug. 07, 2003.
Claims priority of application No. 02001178 (EP), filed on Jan. 29, 2002.
Prior Publication US 2005/0191243 A1, Sep. 01, 2005
Int. Cl. A61B 5/055 (2006.01)

U.S. Cl. 424—9.365 [424/9.1; 424/9.3; 424/9.36; 534/15]

14 Claims

1. A method for the determination, by use of the CEST MRI technique, of a physical or chemical parameter selected from temperature, pH, metabolite concentration, O₂or CO₂partial pressure and enzymatic activity in a human or animal body organ, fluid or tissue, wherein:

a responsive paramagnetic CEST contrast agent is administered comprising at least one exchangeable proton whose saturation capability is correlated to the physical or chemical parameter of interest, and

a CEST MR image responsive for said parameter is generated,

the employed CEST contrast agent comprising a paramagnetic chelate compound in which the chelating ligand is a compound of formula (I)

where:


Ligand A
R = R′ = R″ = R′″ = —CH₂—CONH—CH₂COOH
Ligand B
R = R′ = R″ = R′″ = —CH₂—CONHNH₂

Ligand C
R = R′ = R″ = —CH₂—CONH₂


Ligand D
R = R′ = R″ = —CH₂—CONH₂


Ligand E
R = R′ = R″ = —CH₂—CONH₂


Ligand F
R = R′ = R″ = —CH₂—CONH—CH₂—COOBu


Ligand G
R = R′ = R″ = —CH₂—CONH₂


Ligand H
R = R′ = R″ = —CH₂—CONH₂


Ligand L
R = R′ = R″ = —CH₂—CONH—CH₂COOH

and the paramagnetic ion is selected from the group consisting of iron (II) (high spin), iron (III), cobalt (II), copper (II), nickel (II), praseodymium (III), neodymium (III), dysprosium (III), erbium (III), terbium (III), holmium (III), thulium (III), ytterbium (III), and europium (III), or a physiological acceptable salt thereof.