Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent.
OBJECTIVE
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 alpha 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 beta 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.
Wang
Xinghe
X
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Feng
Yi
Y
Ke
Tianyi
T
Schabel
Matthias
M
Lu
Zheng-Rong
ZR
D000818:Animals; D001673:Biodegradation, Environmental; D003287:Contrast Media / Q000493:pharmacokinetics*; D003538:Cystamine / Q000737:chemistry; D005682:Gadolinium / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D019786:Gadolinium DTPA / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D011108:Polymers / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003287:Contrast Media; D011108:Polymers; D005682:Gadolinium; D019786:Gadolinium DTPA; D003538:Cystamine