Development of Radiolabeled Membrane Type-1 Matrix Metalloproteinase Activatable Cell Penetrating Peptide Imaging Probes

Molecules

Sander M. J. van Duijnhoven²  Marc S. Robillard¹  Klaas Nicolay²  Holger Grüll² 

[1] Tagworks Pharmaceuticals, High Tech Campus 11, Eindhoven 5656 AE, The Netherlands; E-Mail:;Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11, Eindhoven 5656 AE, The Netherlands; E-Mails:

关键词: molecular imaging;    activatable cell penetrating peptide;    matrix metalloproteinase-14;    membrane type-1 matrix metalloproteinase;    radiolabeling;    myocardial infarction;    peptide chemistry;   

DOI  :  10.3390/molecules200712076

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.