Synthesis and Characterization of Poly(L-glutamic acid) Gadolinium Chelate: A New Biodegradable MRI Contrast Agent

详细信息    查看全文

• 作者：Xiaoxia Wen ; Edward F. Jackson ; Roger E. Price ; E. Edmund Kim ; Qingping Wu ; Sidney Wallace ; Chusilp Charnsangavej ; Juri G. Gelovani ; and Chun Li
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：November 2004
• 年：2004
• 卷：15
• 期：6
• 页码：1408 - 1415
• 全文大小：313K
• 年卷期：v.15,no.6(November 2004)
• ISSN：1520-4812

文摘

Most currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) arenot biodegradable. The goal of this study is to synthesize and characterize poly(L-glutamic acid) (PG)gadolinium chelates as biodegradable blood-pool MRI contrast agents. Two PG chelates of gadoliniumdiethylenetriaminepentaacetic acid (Gd-DTPA) were synthesized through the use of difunctional andmonofunctional DTPA precursors. The conjugates were characterized with regard to molecular weightand molecular weight distribution, gadolinium content, relaxivity, and degradability. Distributionsof the polymeric MRI contrast agents in various organs were determined by intravenous injection of¹¹¹In-labeled polymers into mice bearing murine breast tumors. MRI scans were performed at 1.5 Tin mice after bolus injection of the polymeric chelates. PG-Hex-DTPA-Gd, obtained from aminohexyl-substituted PG and DTPA-dianhydride, was partially cross-linked and was undegradable in thepresence of cathepsin B. On the other hand, PG-Bz-DTPA-Gd synthesized directly from PG andmonofunctional p-aminobenzyl-DTPA(acetic acid-tert-butyl ester) was a linear polymer and wasdegradable. The relaxivities of the polymers at 1.5 T were 3-8 times as great as that of Gd-DTPA.Both polymers had high blood concentrations and were primarily accumulated in the kidney. However,PG-Bz-DTPA-Gd was gradually cleared from the body and had significantly less retention in the blood,the spleen, and the kidney. MRI with PG-Bz-DTPA-Gd in mice showed enhanced vascular contrastat up to 2 h after the contrast agent injection. The ability of PG-Bz-DTPA-Gd to be degraded andcleared from the body makes it a favorable macromolecular MRI contrast agent.