Title | Modification of Gd-DTPA cystine copolymers with PEG-1000 optimizes pharmacokinetics and tissue retention for magnetic resonance angiography. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Mohs AM, Nguyen T, Jeong E-K, Feng Y, Emerson L, Zong Y, Parker DL, Lu Z-R |
Journal | Magn Reson Med |
Volume | 58 |
Issue | 1 |
Pagination | 110-8 |
Date Published | 2007 Jul |
ISSN | 0740-3194 |
Keywords | Animals, Contrast Media, Cystine, Gadolinium DTPA, Kidney, Liver, Magnetic Resonance Angiography, Polyethylene Glycols, Polymers, Rats, Rats, Sprague-Dawley |
Abstract | The purpose of this study was to investigate the effect of PEGylation of novel biodegradable macromolecular polydisulfide Gd(III) complexes, gadolinium diethylenetriaminepentaacetate (GdDTPA) cystine copolymers (GDCP), on their pharmacokinetics and long-term Gd(III) tissue retention, and to demonstrate the potential application of PEGylated GDCP (PEG-GDCP) for MR angiography (MRA). The pharmacokinetics, biodistribution, and metabolic excretion of PEG(1000)-GDCP (42.1-52.1 kDa; PEG: MW = 1000 Da) with three different PEG grafting degrees and GDCP (43.3 kDa) were investigated in Sprague-Dawley rats. Pharmacokinetic data were analyzed by means of an open two-compartment model. Initially all three PEG(1000)-GDCP contrast agents (CAs) had a higher plasma concentration than GDCP, but after 30 min the Gd(III) concentration from the PEGylated agents rapidly decreased, resulting in significantly lower elimination half-life values. All of the biodegradable macromolecular CAs demonstrated low long-term Gd(III) tissue accumulation, while PEG(1000)-GDCP had significantly lower accumulation in the liver than GDCP. In the rats, all CAs showed excellent vascular contrast enhancement in an MRA protocol with a long image acquisition time. Because PEG(1000)-GDCP remained intravascular for an acceptable period for effective contrast-enhanced (CE)-MRA, and then excreted rapidly from the vasculature with minimal tissue retention, PEG(1000)-GDCP shows a great promise as a blood-pool CA for MRA. |
DOI | 10.1002/mrm.21270 |
Alternate Journal | Magn Reson Med |
PubMed ID | 17659618 |
Grant List | R01EB00489 / EB / NIBIB NIH HHS / United States |
Related Institute:
MRI Research Institute (MRIRI)