Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.
Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.
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DOI：
10.1021/jm4012565
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发表时间：
2013-10-24
影响因子：
7.3
通讯作者：
Tsourkas A
中科院分区：
文献类型：
--
作者：
Nwe K;Huang CH;Tsourkas A
肿瘤性病变会产生细胞外 pH 值较低的恶劣肿瘤微环境。人们普遍认为这些情况会导致肿瘤进展和对治疗的抵抗。我们报告了 pH 响应磁共振成像造影剂的开发和表征，用于对酸性肿瘤微环境进行成像。该制备方法包括将 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸 1-(2,5-二氧代-1-吡咯烷基) 酯 (DOTA-NHS) 缀合到水溶性乙二醇壳聚糖 (GC) 聚合物的表面，该聚合物含有 pH 可滴定的伯胺，然后进行钆络合 (GC-NH2-GdDOTA)。 GC-NH2-GdDOTA 的螯合物与聚合物的比例约为 1:24，摩尔弛豫率为 9.1 mM−1s−1。与对照相比，GC-NH2-GdDOTA 在体外表现出 pH 依赖性细胞关联。注射后 2 小时，荷瘤小鼠的信号也增强了 2.4 倍。这些发现表明乙二醇壳聚糖与造影剂结合可以提供有关肿瘤微环境的重要诊断信息。
Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression and resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent, for imaging the acidic tumor microenvironment. The preparation included conjugation of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water soluble glycol chitosan (GC) polymer, which contains pH titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate to polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM−1s−1. GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor bearing mice 2 h post-injection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.
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影响因子：
8.8
作者：
Bhujwalla ZM;McCoy CL;Glickson JD;Gillies RJ;Stubbs M
通讯作者：
Stubbs M
影响因子：
120.7
作者：
Bluemke, DA;Gatsonis, CA;Schnall, MD
通讯作者：
Schnall, MD
影响因子：
3.3
作者：
BRASCH, RC
通讯作者：
BRASCH, RC
影响因子：
19.7
作者：
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通讯作者：
ROSATO, EF
DOI：
10.1016/j.bbagen.2006.12.003
发表时间：
2007-04-01
影响因子：
3
作者：
Kumar, Acharya B. Vishu;Varadaraj, Mandyam C.;Tharanathan, Rudrapatnam N.
通讯作者：
Tharanathan, Rudrapatnam N.