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Pharmacokinetics and Tissue Retention of (Gd-DTPA)-Cystamine Copolymers, a Biodegradable Macromolecular Magnetic Resonance Imaging Contrast Agent

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Purpose.

To investigate the pharmacokinetics, long-term tissue retention of Gd(III) ions, and magnetic resonance imaging (MRI) contrast enhancement of extracellular biodegradable macromolecular Gd(III) complexes, (Gd-DTPA)-cystamine copolymers (GDCC), of different molecular weights.

Methods.

The pharmacokinetics of blood clearance and long-term Gd(III) retention of GDCC were investigated in Sprague-Dawley rats. Pharmacokinetic parameters were calculated by using a two-compartment model. The blood pool contrast enhancement of GDCC was evaluated in Sprague-Dawley rats on a Siemens Trio 3T MR scanner. Gd-(DTPA-BMA) was used as a control.

Results.

The α phase half-life of Gd-(DTPA-BMA) and GDCC with molecular weights of 18,000 (GDCC-18) and 60,000 Da (GDCC-60) was 0.48 ± 0.16 min, 1.08 ± 0.24 min, and 1.74 ± 0.57 min, and the β phase half-life was 21.2 ± 5.5 min, 26.5 ± 5.9 min, and 53.7 ± 15.9 min, respectively. GDCC had minimal long-term Gd tissue retention comparable to that of Gd-(DTPA-BMA). GDCC resulted in more significant contrast enhancement in the blood pool than Gd-(DTPA-BMA).

Conclusions.

GDCC provides a prolonged blood pool retention time for effective MRI contrast enhancement and then clears rapidly with minimal accumulation of Gd (III) ions. It is promising for further development as a blood pool MRI contrast agent.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112, USA

    Xinghe Wang, Tianyi Ke & Zheng-Rong Lu

  2. Department of Materials Science and Engineering, University of Utah, Salt Lake City, Utah, 84112, USA

    Yi Feng

  3. Department of Radiology, University of Utah, Salt Lake City, Utah, 84112, USA

    Matthias Schabel

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  1. Xinghe Wang
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  2. Yi Feng
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  3. Tianyi Ke
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  4. Matthias Schabel
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  5. Zheng-Rong Lu
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Correspondence to Zheng-Rong Lu.

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Wang, X., Feng, Y., Ke, T. et al. Pharmacokinetics and Tissue Retention of (Gd-DTPA)-Cystamine Copolymers, a Biodegradable Macromolecular Magnetic Resonance Imaging Contrast Agent. Pharm Res 22, 596–602 (2005). https://doi.org/10.1007/s11095-005-2489-7

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  • DOI: https://doi.org/10.1007/s11095-005-2489-7

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