Polyamine dendrimer-based MRI contrast agents for functional kidney imaging to diagnose acute renal failure.
OBJECTIVE
To choose an efficacious renal functional MRI contrast agent to image early renal tubular damage. We synthesized and compared smaller polyamine dendrimer-based MRI contrast agents (<60 kD) that, unlike Gd-[DTPA], transiently accumulate in renal tubules and can be used to visualize renal structural and functional damage.


METHODS
Six dendrimer-based MRI contrast agents smaller than 60 kD were studied by high resolution dynamic micro-MRI and compared to Gd-[DTPA]-dimeglumine and Gadomer-17. The best agent, DAB-G2, was further tested in a mouse ischemia/reperfusion model to validate its efficacy.


RESULTS
Despite unequal renal clearance rates, all polyamine dendrimer agents visualized the renal functional anatomy of the mice better than Gd-[DTPA]-dimeglumine and Gadomer-17. DAB-G2 was excreted most rapidly, yet was able to visualize mild renal tubular injury very early after injury.


CONCLUSIONS
DAB-G2 was found to be the best candidate for functional kidney imaging and enabled early diagnosis of acute renal injury.
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Kobayash@mail.nih.gov
Hisataka
H
Kobayashi
Sang-Kyung
SK
Jo
Satomi
S
Kawamoto
Hideo
H
Yasuda
Xuzhen
X
Hu
Michael V
MV
Knopp
Martin W
MW
Brechbiel
Peter L
PL
Choyke
Robert A
RA
Star
D058186:Acute Kidney Injury / Q000175:diagnosis*; D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D050091:Dendrimers; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D011073:Polyamines / Q000737:chemistry*
D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D019786:Gadolinium DTPA