To develop and characterize a new class of potential blood pool magnetic resonance (MR) contrast agents which could be used as cancer target gene delivery carrier

novel gadolinium amino group terminated poly(ether-urethane-amide)/diethylenetriamine pentaacetic acid (PEU-Gd-DTPA) polymeric chelate（Ⅳ）was synthesized.The amino group terminated poly(ether-urethaneamide)/diethylenetriamine pentaacetic acid (PEU/DTPA) copolymer ligand （Ⅲ）could be designed and obtained from the reaction of diethylenetriamine pentaacetic acid dianhydride (DTPAA

Ⅰ) with amino group terminated PEU (PEU-((CH2)6NH2)2) （Ⅱ）

which was prepared in high yield by the reaction of polyethylene glycol (PEG) with isophorone diisocyanate (IPDI) and then with hexamethylene diamine.Ligand Ⅲ was then coordinated with Gd3+ ion to give the macromolecular contrast agent Ⅳ in water at room temperature.The structure analysis and characterization of DTPAA

Ⅱ

Ⅲ were studied by IR

NMR

GPC

and functional group titration methods.Gadolinium content of the polymeric chelate Ⅳ was 088 wt%

which was determined by radio frequency inductively coupled plasma (ICP) spectra.In vitro- relaxivity (R1) studies of Ⅳ showed a 38.40% increase in R1 relaxivity compared with gadoliniumdiethylenetriamine pentaacetic acid dimeglumine (Gd-DTPA) injection.The R1 values for Gd-DTPA and Ⅳ were 5.93 and 8.21(mmol/L)-1#8226;s-1

respectively.In vivo distribution of Gd-DTPA and Ⅳ was studied at magnetic resonance imaging (MRI) before injection

0.1

6

12 and 24 h after injection

with assessment of liver signal intensity (SI) in 10 nude mice.The liver signal enhancement rates of Ⅳ at 0.1

6

12 and 24 h are 1.5

3

1.8 and 1.3 times

respectively

compared with the largest signal intensity 0.33 of GdDTPA observed at 0.1 h.The half-life of Ⅳ in liver was as longer as 24 h

while no signal enhancement was observed after 6 hours injection of Gd-DTPA.Ⅳ had also a longer circulation life.