Methods for functional kidney imaging using dendrimer...

A - Human Necessities – 61 – K

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Details

IPC codes

A61K 49/12 (2006.01) A61K 49/08 (2006.01)

Type

Patent

Patent number

CA 2496802

Description

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. Suprisingly, 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.

La présente invention concerne de petits agents de contraste IRM à base de dendrimères qui s'accumulent dans les tubules rénaux.L'accumulation de ces derniers permet de visualiser la structure et la fonction rénales et, par conséquent, d'évaluer les dommages structurels et fonctionnels des reins. Dans un mode de réalisation, l'invention porte sur six petits agents de contraste IRM à base de dendrimères qui ont été synthétisés, et dont on a évalué la pharmacocinétique, la rétention corporelle totale et les images IRM rénales chez les souris. Etonnament, malgré des propriétés de clairance rénale inégales, tous les agents dendrimères ont permis de clairement visualiser l'anatomie rénale et les tubules droits proximaux des souris mieux que la Gd-ÝDTPA¨-diméglumine. Des agents de contraste conjugués dendrimères préparés à partir de PAMAM-G2D, DAB-G3D, et DAB-G2D ont été excrétés rapidement et se sont révélés acceptables dans des applications cliniques.

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