Development of Radiolabeled Membrane Type-1 Matrix Metalloproteinase Activatable Cell Penetrating Peptide Imaging Probes.
Molecules
; 20(7): 12076-92, 2015 Jul 02.
Article
in En
| MEDLINE
| ID: mdl-26147581
ABSTRACT
Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevated MT1-MMP levels in adverse cardiac remodelling. Three ACPP analogs were synthesized and the most potent ACPP analog was selected using MT1-MMP sensitivity and enzyme specificity assays. This ACPP, called ACPP-B, showed high sensitivity towards MT1-MMP, soluble MMP-2, and MT2-MMP, while limited sensitivity was measured for other members of the MMP family. In in vitro cell assays, radiolabeled ACPP-B showed efficient cellular uptake upon activation. A pilot in vivo study showed increased uptake of the radiolabeled probe in regions of infarcted myocardium compared to remote myocardium, warranting further in vivo evaluation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radioisotopes
/
Molecular Probes
/
Matrix Metalloproteinase 14
/
Cell-Penetrating Peptides
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2015
Type:
Article
Affiliation country:
Netherlands