Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent

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• 作者：Minnie Chan ; Jacques Lux ; Tomoki Nishimura ; Kazunari Akiyoshi ; Adah Almutairi
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：September 14, 2015
• 年：2015
• 卷：16
• 期：9
• 页码：2964-2971
• 全文大小：569K
• ISSN：1526-4602

文摘

Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd-CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio.