A PARACEST MRI contrast agent to detect enzyme activity

被引:154
作者
Yoo, Byunghee [1 ]
Pagel, Marty D. [1 ]
机构
[1] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA
关键词
D O I
10.1021/ja063874f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A "smart" PARACEST MRI contrast agent was synthesized to detect caspase-3, which is an important biomarker in apoptosis. The well-known caspase-3 substrate, DEVD (Asp-Glu-Val-Asp), was elongated using the amino group on one sidearm of lanthanide ligand anchored on the polymer support. The amide of DEVD-(Tm-DOTA) showed a PARACEST effect with MR saturation at -51 ppm. DEVD-(Tm-DOTA) amide was successfully cleaved by caspase-3, exposing the free amine group, which showed PARACEST with saturation at +8 ppm. The enzymatic activity of caspase-3 can be detected by the change in PARACEST effect caused by this biotransformation. Copyright © 2006 American Chemical Society.
引用
收藏
页码:14032 / 14033
页数:2
相关论文
共 19 条
[1]   A model for MRI contrast enhancement using T1 agents [J].
Ahrens, ET ;
Rothbächer, U ;
Jacobs, RE ;
Fraser, SE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8443-8448
[2]   Supramolecular adducts between poly-L-arginine and [TmIIIdotp]:: A route to sensitivity-enhanced magnetic resonance imaging-chemical exchange saturation transfer agents [J].
Aime, S ;
Delli Castelli, D ;
Terreno, E .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (37) :4527-4529
[3]  
Aime S, 2002, ANGEW CHEM INT EDIT, V41, P4334, DOI 10.1002/1521-3773(20021115)41:22<4334::AID-ANIE4334>3.0.CO
[4]  
2-1
[5]   Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications [J].
Aime, S ;
Barge, A ;
Delli Castelli, D ;
Fedeli, F ;
Mortillaro, A ;
Nielsen, FU ;
Terreno, E .
MAGNETIC RESONANCE IN MEDICINE, 2002, 47 (04) :639-648
[6]   A paramagnetic MRI-CEST agent responsive to lactate concentration [J].
Aime, S ;
Delli Castelli, D ;
Fedeli, F ;
Terreno, E .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (32) :9364-9365
[7]   Heavy membrane-associated caspase 3. Identification, isolation, and characterization [J].
Krebs, JF ;
Srinivasan, A ;
Wong, AM ;
Tomaselli, KJ ;
Fritz, LC ;
Wu, JC .
BIOCHEMISTRY, 2000, 39 (51) :16056-16063
[8]   Proton exchange rates from amino acid side chains - Implications for image contrast [J].
Liepinsh, E ;
Otting, G .
MAGNETIC RESONANCE IN MEDICINE, 1996, 35 (01) :30-42
[9]   DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis [J].
Liu, XS ;
Zou, H ;
Slaughter, C ;
Wang, XD .
CELL, 1997, 89 (02) :175-184
[10]   In vivo visualization of gene expression using magnetic resonance imaging [J].
Louie, AY ;
Hüber, MM ;
Ahrens, ET ;
Rothbächer, U ;
Moats, R ;
Jacobs, RE ;
Fraser, SE ;
Meade, TJ .
NATURE BIOTECHNOLOGY, 2000, 18 (03) :321-325