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

Fingerprint

Atherosclerotic Plaques
Magnetic resonance
Contrast Media
magnetic resonance
Magnetic Resonance Imaging
Imaging techniques
Molecules
molecules
lipids
Biological Phenomena
aorta
rabbits
Lipids
Gadolinium
gadolinium
Adipocytes
Fluorophores
Intravenous Injections
Aorta
Coloring Agents

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry
  • Medicine(all)

Cite this

A design strategy for small molecule-based targeted MRI contrast agents : Their application for detection of atherosclerotic plaques. / Iwaki, Shimpei; Hokamura, Kazuya; Ogawa, Mikako; Takehara, Yasuo; Muramatsu, Yasuaki; Yamane, Takehiro; Hirabayashi, Kazuhisa; Morimoto, Yuji; Hagisawa, Kohsuke; Nakahara, Kazuhide; Mineno, Tomoko; Terai, Takuya; Komatsu, Toru; Ueno, Tasuku; Tamura, Keita; Adachi, Yusuke; Hirata, Yasunobu; Arita, Makoto; Arai, Hiroyuki; Umemura, Kazuo; Nagano, Tetsuo; Hanaoka, Kenjiro.

In: Organic and Biomolecular Chemistry, Vol. 12, No. 43, 21.11.2014, p. 8611-8618.

Research output: Contribution to journalArticle

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, Umemura, K, Nagano, T & 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, vol. 12, no. 43, pp. 8611-8618. https://doi.org/10.1039/c4ob01270d
Iwaki, Shimpei ; Hokamura, Kazuya ; Ogawa, Mikako ; Takehara, Yasuo ; Muramatsu, Yasuaki ; Yamane, Takehiro ; Hirabayashi, Kazuhisa ; Morimoto, Yuji ; Hagisawa, Kohsuke ; Nakahara, Kazuhide ; Mineno, Tomoko ; Terai, Takuya ; Komatsu, Toru ; Ueno, Tasuku ; Tamura, Keita ; Adachi, Yusuke ; Hirata, Yasunobu ; Arita, Makoto ; Arai, Hiroyuki ; Umemura, Kazuo ; Nagano, Tetsuo ; Hanaoka, Kenjiro. / A design strategy for small molecule-based targeted MRI contrast agents : Their application for detection of atherosclerotic plaques. In: Organic and Biomolecular Chemistry. 2014 ; Vol. 12, No. 43. pp. 8611-8618.
@article{4dcab7a815384654a21fb560c1edcfc9,
title = "A design strategy for small molecule-based targeted MRI contrast agents: Their application for detection of atherosclerotic plaques",
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.",
author = "Shimpei Iwaki and Kazuya Hokamura and Mikako Ogawa and Yasuo Takehara and Yasuaki Muramatsu and Takehiro Yamane and Kazuhisa Hirabayashi and Yuji Morimoto and Kohsuke Hagisawa and Kazuhide Nakahara and Tomoko Mineno and Takuya Terai and Toru Komatsu and Tasuku Ueno and Keita Tamura and Yusuke Adachi and Yasunobu Hirata and Makoto Arita and Hiroyuki Arai and Kazuo Umemura and Tetsuo Nagano and Kenjiro Hanaoka",
year = "2014",
month = "11",
day = "21",
doi = "10.1039/c4ob01270d",
language = "English",
volume = "12",
pages = "8611--8618",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "43",

}

TY - JOUR

T1 - A design strategy for small molecule-based targeted MRI contrast agents

T2 - Their application for detection of atherosclerotic plaques

AU - Iwaki, Shimpei

AU - Hokamura, Kazuya

AU - Ogawa, Mikako

AU - Takehara, Yasuo

AU - Muramatsu, Yasuaki

AU - Yamane, Takehiro

AU - Hirabayashi, Kazuhisa

AU - Morimoto, Yuji

AU - Hagisawa, Kohsuke

AU - Nakahara, Kazuhide

AU - Mineno, Tomoko

AU - Terai, Takuya

AU - Komatsu, Toru

AU - Ueno, Tasuku

AU - Tamura, Keita

AU - Adachi, Yusuke

AU - Hirata, Yasunobu

AU - Arita, Makoto

AU - Arai, Hiroyuki

AU - Umemura, Kazuo

AU - Nagano, Tetsuo

AU - Hanaoka, Kenjiro

PY - 2014/11/21

Y1 - 2014/11/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907992914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907992914&partnerID=8YFLogxK

U2 - 10.1039/c4ob01270d

DO - 10.1039/c4ob01270d

M3 - Article

C2 - 25186130

AN - SCOPUS:84907992914

VL - 12

SP - 8611

EP - 8618

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 43

ER -