Toward Improved Syntheses of Dendrimer-Based Magnetic Resonance Imaging Contrast Agents: New Bifunctional Diethylenetriaminepentaacetic Acid Ligands and Nonaqueous Conjugation Chemistry

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• 作者：Heng Xu ; Celeste A. S. Regino ; Marcelino Bernardo ; Yoshinori Koyama ; Hisataka Kobayashi ; Peter L. Choyke ; Martin W. Brechbiel
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：July 12, 2007
• 年：2007
• 卷：50
• 期：14
• 页码：3185 - 3193
• 全文大小：380K
• 年卷期：v.50,no.14(July 12, 2007)
• ISSN：1520-4804

文摘

Two different fourth-generation (G4) polyaminonamido dendrimer-based magnetic resonsance (MR) agentswere prepared by a new synthetic approach wherein tert-butyl-protected forms of 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriamine pentaacetic acid (1B4M-DTPA), bearing either an isothiocyanate or a succinimidylester moiety, respectively, were conjugated to the primary amines of the dendrimer. Purification was facilitatedusing a solid phase, N-(2-aminoethyl)aminomethyl polystyrene. After Gd(III) incorporation, molar relaxivitymeasurements of both new dendrimer-based agents as compared to a G4 agent prepared by an aqueouschemistry route indicated no significant changes in relaxivity. Comparative MR imaging revealed equivalentenhancement of the vessels and organs such as the kidney and liver, although slightly different vascularclearance rates were observed. This general synthesis provides a procedure for preparation of dendrimer-based MR agents for clinical applications with higher yields and efficiency while enhancing versatility. Thelatter aspect is further demonstrated by preparation of a novel maleimide analog of 1B4M-DTPA from akey synthetic intermediate aniline derivative.