Modification of Gd-DTPA cystine copolymers with PEG-1000 optimizes pharmacokinetics and tissue retention for magnetic resonance angiography

Aaron M. Mohs, Thanh Nguyen, Eun Kee Jeong, Yi Feng, Lyska Emerson, Yuda Zong, Dennis L. Parker, Zheng Rong Lu

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalMagnetic Resonance in Medicine
Volume58
Issue number1
DOIs
StatePublished - Jul 1 2007

Fingerprint

Cystine
Magnetic Resonance Angiography
Pharmacokinetics
Contrast Media
Angiography
polyethylene glycol 1000
gadolinium-DTPA cystine copolymer
Gadolinium
Blood Vessels
Sprague Dawley Rats
Half-Life

Keywords

  • Contrast agent
  • Gadolinium
  • MRA
  • Poly(ethylene glycol)
  • Polydisulfide

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Modification of Gd-DTPA cystine copolymers with PEG-1000 optimizes pharmacokinetics and tissue retention for magnetic resonance angiography. / Mohs, Aaron M.; Nguyen, Thanh; Jeong, Eun Kee; Feng, Yi; Emerson, Lyska; Zong, Yuda; Parker, Dennis L.; Lu, Zheng Rong.

In: Magnetic Resonance in Medicine, Vol. 58, No. 1, 01.07.2007, p. 110-118.

Research output: Contribution to journalArticle

Mohs, Aaron M. ; Nguyen, Thanh ; Jeong, Eun Kee ; Feng, Yi ; Emerson, Lyska ; Zong, Yuda ; Parker, Dennis L. ; Lu, Zheng Rong. / Modification of Gd-DTPA cystine copolymers with PEG-1000 optimizes pharmacokinetics and tissue retention for magnetic resonance angiography. In: Magnetic Resonance in Medicine. 2007 ; Vol. 58, No. 1. pp. 110-118.
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