| 主权项 |
1. A protein contrast agent for enhancing an MRI image, the protein contrast agent comprising:
(i) a polypeptide having a conformation presenting at least five oxygen atoms positioned to chelate at least one paramagnetic metal ion selected from the group consisting of Gd3+, Eu3+, Tm3+, Yb3+, Lu3+, Mn2+, and Fe3+, and wherein (a) each oxygen atom interacting with the metal ion is between about 2 angstrom units and about 5 angstrom units from the metal ion; (b) the metal ion has at least one water molecule electrostatically interacting therewith and at a distance of less than about 10 angstrom units therefrom, and wherein the polypeptide includes a target-specific moiety attached thereto; (ii) at least one polyethylene glycol molecule attached to the polypeptide; and (iii) at least one paramagnetic metal ion chelated to the polypeptide,wherein the protein contrast agent, when administered to a human or non-human animal provides an enhanced MRI image allowing the determination of a T2/T1 or T1/T2 MRI intensity ratio, and wherein the metal ion or ions are chelated to a beta-fold region of the polypeptide or at least one loop and an alpha-helix, wherein the protein contrast agent can provide an image of a tumor having a size less than about 0.25 microns, and wherein the target-specific moiety is specific for a cell-specific target selected from the group consisting of: a hepatic tumor, a renal tumor, and a cardiovascular-specific target, and wherein the protein contrast agent has an amino acid sequence having at least 85% similarity to a sequence selected from the group consisting of: SEQ ID Nos.: 1-22, or conservative variants thereof. |
