PEG-g-poly(GdDTPA-co-L-cystine): Effect of PEG Chain Length on in Vivo Contrast Enhancement in MRI

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• 作者：Aaron M. Mohs ; Yuda Zong ; Junyu Guo ; Dennis L. Parker ; and Zheng-Rong Lu
• 刊名：Biomacromolecules
• 出版年：2005
• 出版时间：July 2005
• 年：2005
• 卷：6
• 期：4
• 页码：2305 - 2311
• 全文大小：243K
• 年卷期：v.6,no.4(July 2005)
• ISSN：1526-4602

文摘

Biodegradable macromolecular Gd(III) complexes, Gd-DTPA cystine copolymers (GDCP), were graftedwith PEG of different sizes to modify the physicochemical properties and in vivo MRI contrast enhancementof the agents and to study the effect of PEG chain length on these properties. Three new PEG-graftedbiodegradable macromolecular gadolinium(III) complexes were synthesized and characterized as blood poolMRI contrast agents. One of three different lengths of MPEG-NH₂ (MW = 550, 1000, and 2000) wasgrafted to the backbone of GDCP to yield PEG_n-g-poly(GdDTPA-co-L-cystine), PEG_n-GDCP. The PEGchain length did not dramatically alter the T₁ relaxivity, r₁, of the modified agents. The MRI enhancementprofile of PEG_n-GDCP with different PEG sizes was significantly different in mice with respect to bothsignal intensity and clearance profiles. PEG₂₀₀₀-GDCP showed more prominent enhancement in the bloodpool for a longer period of time than either PEG₁₀₀₀-GDCP or PEG₅₅₀-GDCP. In the kidney, PEG₂₀₀₀-GDCP had less enhancement at 2 min than PEG₁₀₀₀-GDCP, but both PEG₅₅₀-GDCP and PEG₁₀₀₀-GDCPshowed a more pronounced signal decay thereafter. The three agents behaved similarly in the liver, ascompared to that in the heart. All three agents showed little enhancement in the muscle. Chemical graftingwith PEG of different chain lengths is an effective approach to modify the physiochemistry and in vivocontrast enhancement dynamics of the biodegradable macromolecular contrast agents. The novel agents arepromising for further clinical development for cardiovascular and cancer MR imaging.