Journal
INVESTIGATIVE RADIOLOGY
Volume 38, Issue 10, Pages 662-668Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.rli.0000084887.47427.75
Keywords
macromolecule; MRI contrast agent; dendrimer; gadolinium-DTPA; biodistribution
Funding
- NCRR NIH HHS [5 P41 RR05964, IS10RR06243] Funding Source: Medline
- PHS HHS [1 R29 C61918] Funding Source: Medline
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Rationale and objectives: Dendrimer-based magnetic resonance imaging (MRI) contrast agents offer many advantages including high levels of amplification. The objective of this research was to test the adequacy and viability of a new family of dendrimers for use as MRI contrast agents in vitro and in vivo. Methods: Dendrimers based on 1,4-diaminobutane core polypropyleneimine (PPI) generation 2 and ammonia core polyamidoamine dendrimers had the free surface amines conjugated to a diethylenetriaminepentaacetic acid derivative followed by complex formation with gadolinium. Relaxivity measurements were made on an IBM Field Cycling Relaxometer. Biodistribution and pharmacokinetic studies were examined with the radiotracer Gd-153 in rats and a counting window of 95 to 105 keV. MRI images were conducted at 4.7 T. Results: The relaxivity of the PPI agent exceeded that of the corresponding generation polyamidoamine (PAMAM) agent. Uptake occurred in the liver, spleen, and kidney. Pharmacokinetic studies showed a biexponential decay with excretion half-lives of 3 hours and 33.6 days respectively. The agent increased the contrast enhancement, 1 hour after injection, of T1-weighted images by 52%. Conclusions: This PPI agent resulted in significant contrast signal enhancement. This family of agent may also provide a valuable contrast agent backbone.
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