Document Detail

Activatable near-infrared fluorescent probe for in vivo imaging of fibroblast activation protein-alpha.
MedLine Citation:
PMID:  22812530     Owner:  NLM     Status:  MEDLINE    
Fibroblast activation protein-alpha (FAPα) is a cell surface glycoprotein which is selectively expressed by tumor-associated fibroblasts in malignant tumors but rarely on normal tissues. FAPα has also been reported to promote tumor growth and invasion and therefore has been of increasing interest as a promising target for designing tumor-targeted drugs and imaging agents. Although medicinal study on FAPα inhibitors has led to the discovery of many FAPα-targeting inhibitors including a drug candidate in a phase II clinical trial, the development of imaging probes to monitor the expression and activity of FAPα in vivo has largely lagged behind. Herein, we report an activatable near-infrared (NIR) fluorescent probe (ANP(FAP)) for in vivo optical imaging of FAPα. The ANP(FAP) consists of a NIR dye (Cy5.5) and a quencher dye (QSY21) which are linked together by a short peptide sequence (KGPGPNQC) specific for FAPα cleavage. Because of the efficient fluorescence resonance energy transfer (FRET) between Cy5.5 and QSY21 in ANP(FAP), high contrast on the NIR fluorescence signal can be achieved after the cleavage of the peptide sequence by FAPα both in vitro and in vivo. In vitro assay on ANP(FAP) indicated the specificity of the probe to FAPα. The in vivo optical imaging using ANP(FAP) showed fast tumor uptake as well as high tumor to background contrast on U87MG tumor models with FAPα expression, while much lower signal and tumor contrast were observed in the C6 tumor without FAPα expression, demonstrating the in vivo targeting specificity of the ANP(FAP). Ex vivo imaging also demonstrated ANP(FAP) had high tumor uptake at 4 h post injection. Collectively, these results indicated that ANP(FAP) could serve as a useful NIR optical probe for early detection of FAPα expressing tumors.
Jinbo Li; Kai Chen; Hongguang Liu; Kai Cheng; Meng Yang; Jiping Zhang; Jonathan D Cheng; Yan Zhang; Zhen Cheng
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-31
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  23     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2012-12-21     Revised Date:  2013-08-19    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1704-11     Citation Subset:  IM    
Molecular Imaging Program at Stanford (MIPS), Department of Radiology, and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305-5344, USA.
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MeSH Terms
Amino Acid Sequence
Carbocyanines / chemistry
Cell Line, Tumor
Drug Design
Fluorescent Dyes / chemical synthesis,  chemistry*,  diagnostic use*,  metabolism
Gelatinases / chemistry,  metabolism*
Gene Expression Regulation, Neoplastic
Infrared Rays*
Membrane Proteins / chemistry,  metabolism*
Molecular Imaging / methods*
Optical Imaging
Serine Endopeptidases / chemistry,  metabolism*
Substrate Specificity
Grant Support
5R01 CA119053/CA/NCI NIH HHS; R01 CA119053/CA/NCI NIH HHS
Reg. No./Substance:
0/CY5.5 cyanine dye; 0/Carbocyanines; 0/Fluorescent Dyes; 0/Membrane Proteins; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/fibroblast activation protein alpha; EC 3.4.24.-/Gelatinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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