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 PEG1000-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 PEG1000-GDCP remained intravascular for an acceptable period for effective contrast-enhanced (CE)-MRA, and then excreted rapidly from the vasculature with minimal tissue retention, PEG1000-GDCP shows a great promise as a blood-pool CA for MRA.
- Contrast agent
- Poly(ethylene glycol)
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging