Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent.
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.
Minnie
M
Chan
Jacques
J
Lux
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura , Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bionanotransporter Project, Katsura Int'tech Center, Katsura , Nishikyo-ku, Kyoto 615-8530, Japan.
Tomoki
T
Nishimura
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura , Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bionanotransporter Project, Katsura Int'tech Center, Katsura , Nishikyo-ku, Kyoto 615-8530, Japan.
Kazunari
K
Akiyoshi
Adah
A
Almutairi
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005682:Gadolinium / Q000737:chemistry / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D011859:Radiography
D003287:Contrast Media; D011134:Polysaccharides; D005682:Gadolinium