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

• Main Authors: Sander M. J. van Duijnhoven, Marc S. Robillard, Klaas Nicolay, Holger Grüll
• Format: Article
• Language: English
• Published: MDPI AG 2015-07-01
• Series: Molecules
• Subjects: molecular imaging; activatable cell penetrating peptide; matrix metalloproteinase-14; membrane type-1 matrix metalloproteinase; radiolabeling; myocardial infarction; peptide chemistry
• Online Access: http://www.mdpi.com/1420-3049/20/7/12076

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.