A Gd3+-based magnetic resonance imaging contrast agent sensitive to β-Galactosidase activity utilizing a receptor-induced magnetization enhancement (RIME) phenomenon

Kenjiro Hanaoka, Kazuya Kikuchi, Takuya Terai, Toru Komatsu, Tetsuo Nagano

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging of opaque organisms. Gadolinium (Gd3+) complexes have become important imaging tools as MRI contrast agents for MRI studies, though most of them are nonspecific and report solely on anatomy. Recently, MRI contrast agents have been reported whose ability to relax water protons is triggered or greatly enhanced by recognition of a particular biomolecule. This new class of MRI contrast agents could open up the possibility of reporting on the physiological state or metabolic activity deep within living specimens. One possible strategy for this purpose is to utilize the increase in the longitudinal water proton r1 relaxivity that occurs upon slowing the molecular rotation of a small paramagnetic complex, a phenomenon which is known as receptor-induced magnetization enhancement (RIME), by either binding to a macro-molecule or polymerization of the agent itself. Here we describe the design and synthesis of a novel β-galactosidase-activated MRI contrast agent, the Gd3+ complex [Gd-5], by using the RIME approach. β-Galactosidase is commonly used as a marker gene to monitor gene expression. This newly synthesized compound exhibited a 57% increase in the r1 relaxivity in phosphate-buffered saline (PBS) with 4.5% w/v human serum albumin (HSA) in the presence of β-galactosidase. Detailed investigations revealed that RIME is the dominant factor in this increase of the observed r1 relaxivity, based on analysis of Gd3+ complexes [Gd-5] and [Gd-8], which is generated from [Gd-5] by the activity of β-galactosidase, and spectroscopic analysis of their corresponding Tb3+ complexes, [Tb-5] and [Tb-8].

Original languageEnglish
Pages (from-to)987-995
Number of pages9
JournalChemistry - A European Journal
Volume14
Issue number3
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Biosensors
  • Gadolinium complexes
  • Lanthanides
  • Luminescence
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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