Methods for functional kidney imaging using small dendrimer contrast agents
First Claim
1. A dendrimer conjugate, comprising:
- a dendrimer selected from the group consisting of DAB-G2D and DAB-G3D; and
a gadolinium (III) chelate of 1B4M.
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Accused Products
Abstract
Small dendrimer-based MRI contrast agents are disclosed to accumulate in renal tubules. The accumulation enables visualization of renal structure and function, permitting assessment of structural and functional damage to the kidneys. In a disclosed embodiment, six, small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole body retention, and renal MRI images were evaluated in mice. Surprisingly, despite having unequal renal clearance properties, all of the dendrimer agents clearly visualized the renal anatomy and proximal straight tubules of the mice better than Gd-[DTPA]-dimeglumine. Dendrimer conjugate contrast agents prepared from PAMAM-G2D, DAB-G3D, and DAB-G2D dendrimers were excreted rapidly and may be acceptable for use in clinical applications.
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Citations
49 Claims
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1. A dendrimer conjugate, comprising:
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a dendrimer selected from the group consisting of DAB-G2D and DAB-G3D; and
a gadolinium (III) chelate of 1B4M.
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2. A method for kidney imaging, comprising:
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administering an image enhancing amount of a dendrimer conjugate to a subject, the dendrimer conjugate comprising a dendrimer selected from the group consisting of DAB-G2D, DAB-G3D, DAB-G4D, PAMAM-G2D, PAMAM-G3D and PAMAM-G4D and a metal chelate;
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered; and
measuring a thickness of the cortex and the outer medulla of the kidney in an MRI image to determine if the kidney exhibits thinning associated with chronic renal failure. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method for kidney imaging, comprising:
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administering to a subject an image enhancing amount of a dendrimer conjugate selected from the group consisting of DAB-G2 and DAB-G3, and combinations thereof; and
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22)
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23. A method for kidney imaging, comprising:
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administering an image enhancing amount of a dendrimer conjugate to a subject, the dendrimer conjugate comprising a dendrimer selected from the group consisting of DAB-G2D, DAB-G3D, DAB-G4D, PAMAM-G2D, PAMAM-G3D and PAMAM-G4D and a metal chelate;
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered; and
detecting an image associated with the presence of cysts indicative of chronic renal failure. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
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36. A method for kidney imaging, comprising:
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administering an image enhancing amount of a dendrimer conjugate to a subject, the dendrimer conjugate comprising a dendrimer selected from the group consisting of DAB-G2D and DAB-G3D and a metal chelate; and
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered. - View Dependent Claims (37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
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48. A method for kidney imaging comprising:
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administering to a subject an image enhancing amount of a dendrimer conjugate selected from the group consisting of DAB-G2, DAB-G3, PAMAM-G2 and combinations thereof;
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered; and
measuring a thickness of the cortex and outer medulla of the kidney in an MRI image to determine if the kidney exhibits thinning associated with chronic renal failure.
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49. A method for kidney imaging, comprising:
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administering to a subject an image enhancing amount of a dendrimer conjugate selected from the group consisting of DAB-G2, DAB-G3, PAMAM-G2 and combinations thereof;
detecting a difference in a magnetic resonance signal intensity of at least a portion of the kidney after the dendrimer conjugate is administered; and
detecting an image associated with the presence of cysts indicative of chronic renal failure.
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Specification