TY - JOUR
T1 - Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent
AU - Wang, Xinghe
AU - Feng, Yi
AU - Ke, Tianyi
AU - Schabel, Matthias
AU - Lu, Zheng Rong
N1 - Funding Information:
The research work is supported in part by the NIH grants R21/R33 CA095873 and R01 EB00489. The authors thank Prof. Dennis L. Parker for valuable discussions.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - (Gd-DTPA)-cystamine copolymers
KW - Biodegradable macromolecular contrast agent
KW - Gd tissue accumulation
KW - MRI
KW - Pharmacokinetics
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U2 - 10.1007/s11095-005-2489-7
DO - 10.1007/s11095-005-2489-7
M3 - Article
C2 - 15846467
AN - SCOPUS:18044383907
SN - 0724-8741
VL - 22
SP - 596
EP - 602
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 4
ER -