Development of radiolabeled membrane type-1 matrix metalloproteinase activatable cell penetrating peptide imaging probes

S.M.J. van Duijnhoven, M.S. Robillard, K. Nicolay, H. Grüll

    Research output: Contribution to journalArticleAcademicpeer-review

    5 Citations (Scopus)
    121 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)12076-12092
    Number of pages17
    JournalMolecules
    Volume20
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 2015

    Keywords

    • Activatable cell penetrating peptide
    • Matrix metalloproteinase-14
    • Membrane type-1 matrix metalloproteinase
    • Molecular imaging
    • Myocardial infarction
    • Peptide chemistry
    • Radiolabeling

    Fingerprint

    Dive into the research topics of 'Development of radiolabeled membrane type-1 matrix metalloproteinase activatable cell penetrating peptide imaging probes'. Together they form a unique fingerprint.

    Cite this