title: A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. khanaoka@mol.f.u-tokyo.ac.jp.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Iwaki
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hokamura
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takehara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamane
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Hagisawa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Nakahara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mineno
authors.forename: Takuya
authors.initials: T
authors.lastname: Terai
authors.forename: Toru
authors.initials: T
authors.lastname: Komatsu
authors.forename: Tasuku
authors.initials: T
authors.lastname: Ueno
authors.forename: Keita
authors.initials: K
authors.lastname: Tamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Adachi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umemura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001896:Boron Compounds / Q000737:chemistry*; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry*; D056831:Coordination Complexes / Q000008:administration & dosage / Q000737:chemistry*; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D007275:Injections, Intravenous; D066292:Lipid Droplets / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001057:Apolipoproteins E; D001896:Boron Compounds; D003287:Contrast Media; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D005682:Gadolinium