A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques
| Autor: | Kazuo Umemura, Keita Tamura, Takuya Terai, Shimpei Iwaki, Kazuya Hokamura, Yasuaki Muramatsu, Kohsuke Hagisawa, Kenjiro Hanaoka, Kazuhisa Hirabayashi, Tetsuo Nagano, Makoto Arita, Yuji Morimoto, Hiroyuki Arai, Yasuo Takehara, Yasunobu Hirata, Toru Komatsu, Kazuhide Nakahara, Tomoko Mineno, Yusuke Adachi, Mikako Ogawa, Tasuku Ueno, Takehiro Yamane |
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| Rok vydání: | 2014 |
| Předmět: |
Boron Compounds
Fluorophore MRI contrast agent Gadolinium Contrast Media chemistry.chemical_element Nanotechnology Biochemistry Mice chemistry.chemical_compound Apolipoproteins E Coordination Complexes Lipid droplet Adipocytes medicine Animals Physical and Theoretical Chemistry Aorta Fluorescent Dyes Mice Knockout medicine.diagnostic_test Chemistry Organic Chemistry Magnetic resonance imaging Lipid Droplets Magnetic Resonance Imaging Small molecule Plaque Atherosclerotic Drug Design Injections Intravenous Rabbits BODIPY Preclinical imaging Biomedical engineering |
| Zdroj: | Org. Biomol. Chem.. 12:8611-8618 |
| ISSN: | 1477-0539 1477-0520 |
| DOI: | 10.1039/c4ob01270d |
| Popis: | Gadolinium(III) ion (Gd(3+)) complexes are widely used as contrast agents in magnetic resonance imaging (MRI), and many attempts have been made to couple them to sensor moieties in order to visualize biological phenomena of interest inside the body. However, the low sensitivity of MRI has made it difficult to develop practical MRI contrast agents for in vivo imaging. We hypothesized that practical MRI contrast agents could be designed by targeting a specific biological environment, rather than a specific protein such as a receptor. To test this idea, we designed and synthesized a Gd(3+)-based MRI contrast agent, 2BDP3Gd, for visualizing atherosclerotic plaques by linking the Gd(3+)-complex to the lipophilic fluorophore BODIPY to stain lipid-rich environments. We found that 2BDP3Gd was selectively accumulated into lipid droplets of adipocytes at the cellular level. Atherosclerotic plaques in the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits were clearly visualized in T1-weighted MR images after intravenous injection of 2BDP3Gd in vivo. |
| Databáze: | OpenAIRE |
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