Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes

被引:357
作者
Blum, Galia
von Degenfeld, Georges
Merchant, Milton J.
Blau, Helen M.
Bogyo, Matthew
机构
[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Baxter Lab Genet Pharmacol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
关键词
D O I
10.1038/nchembio.2007.26
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have generated a series of quenched near- infrared fluorescent activity- based probes ( qNIRF- ABPs) that covalently target the papain- family cysteine proteases shown previously to be important in multiple stages of tumorigenesis. These ` smart' probes emit a fluorescent signal only after covalently modifying a specific protease target. After intravenous injection of NIRF- ABPs into mice bearing grafted tumors, noninvasive, whole- body imaging allowed direct monitoring of cathepsin activity. Importantly, the permanent nature of the probes also allowed secondary, ex vivo biochemical profiling to identify specific proteases and to correlate their activity with whole- body images. Finally, we demonstrate that these probes can be used to monitor small- molecule inhibition of protease targets both biochemically and by direct imaging methods. Thus, NIRF- ABPs are ( i) potentially valuable new imaging agents for disease diagnosis and ( ii) powerful tools for preclinical and clinical testing of small- molecule therapeutic agents in vivo.
引用
收藏
页码:668 / 677
页数:10
相关论文
共 40 条
[1]   Enzyme activity - it's all about image [J].
Baruch, A ;
Jeffery, DA ;
Bogyo, M .
TRENDS IN CELL BIOLOGY, 2004, 14 (01) :29-35
[2]  
Berger Alicia B, 2004, Am J Pharmacogenomics, V4, P371, DOI 10.2165/00129785-200404060-00004
[3]   Dynamic imaging of protease activity with fluorescently quenched activity-based probes [J].
Blum, G ;
Mullins, SR ;
Keren, K ;
Fonovic, M ;
Jedeszko, C ;
Rice, MJ ;
Sloane, BF ;
Bogyo, M .
NATURE CHEMICAL BIOLOGY, 2005, 1 (04) :203-209
[4]   Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs [J].
Bogyo, M ;
Verhelst, S ;
Bellingard-Dubouchaud, V ;
Toba, S ;
Greenbaum, D .
CHEMISTRY & BIOLOGY, 2000, 7 (01) :27-38
[5]   Optical imaging of spontaneous breast tumors using protease sensing 'Smart' optical probes [J].
Bremer, C ;
Ntziachristos, V ;
Weitkamp, B ;
Theilmeier, G ;
Heindel, W ;
Weissleder, R .
INVESTIGATIVE RADIOLOGY, 2005, 40 (06) :321-327
[6]  
Choy Garry, 2003, Mol Imaging, V2, P303, DOI 10.1162/153535003322750646
[7]   Substrate specificity of prostate-specific antigen (PSA) [J].
Coombs, GS ;
Bergstrom, RC ;
Pellequer, JL ;
Baker, SI ;
Navre, M ;
Smith, MM ;
Tainer, JA ;
Madison, EL ;
Corey, DR .
CHEMISTRY & BIOLOGY, 1998, 5 (09) :475-488
[8]  
D'Orazi G, 2000, J GENE MED, V2, P11
[9]   Mechanism-based profiling of enzyme families [J].
Evans, Michael J. ;
Cravatt, Benjamin F. .
CHEMICAL REVIEWS, 2006, 106 (08) :3279-3301
[10]   Prognostic significance of cathepsins B and L in primary human breast cancer [J].
Foekens, JA ;
Kos, J ;
Peters, HA ;
Krasovec, M ;
Look, MP ;
Cimerman, N ;
Meijer-van Gelder, ME ;
Henzen-Logmans, SC ;
van Putten, WLJ ;
Klijn, JGM .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (03) :1013-1021