A design strategy for small molecule-based targeted MRI contrast agents: Their application for detection of atherosclerotic plaques

Shimpei Iwaki, Kazuya Hokamura, Mikako Ogawa, Yasuo Takehara, Yasuaki Muramatsu, Takehiro Yamane, Kazuhisa Hirabayashi, Yuji Morimoto, Kohsuke Hagisawa, Kazuhide Nakahara, Tomoko Mineno, Takuya Terai, Toru Komatsu, Tasuku Ueno, Keita Tamura, Yusuke Adachi, Yasunobu Hirata, Makoto Arita, Hiroyuki Arai, Kazuo UmemuraTetsuo Nagano, Kenjiro Hanaoka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Gadolinium(III) ion (Gd3+) 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 Gd3+-based MRI contrast agent, 2BDP3Gd, for visualizing atherosclerotic plaques by linking the Gd3+-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.

Original languageEnglish
Pages (from-to)8611-8618
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number43
DOIs
Publication statusPublished - 2014 Nov 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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    Iwaki, S., Hokamura, K., Ogawa, M., Takehara, Y., Muramatsu, Y., Yamane, T., Hirabayashi, K., Morimoto, Y., Hagisawa, K., Nakahara, K., Mineno, T., Terai, T., Komatsu, T., Ueno, T., Tamura, K., Adachi, Y., Hirata, Y., Arita, M., Arai, H., ... Hanaoka, K. (2014). A design strategy for small molecule-based targeted MRI contrast agents: Their application for detection of atherosclerotic plaques. Organic and Biomolecular Chemistry, 12(43), 8611-8618. https://doi.org/10.1039/c4ob01270d