Probes for Non-invasive Matrix Metalloproteinase-targeted Imaging with PET and SPECT

Nathalie      Matusiak; Aren   van   Waarde; Rainer      Bischoff; Ruth      Oltenfreiter; Christophe van   de   Wiele; Rudi   A.J.O   Dierckx; Philip   H.   Elsinga

doi:10.2174/1381612811319250011

Abstract

Dysregulation of matrix metalloproteinase (MMP) activity can lead to a wide range of disease states such as atherosclerosis, inflammation or cancer. The ability to image MMP activity non-invasively in vivo, by radiolabelled synthetic inhibitors, would allow the characterization of atherosclerotic plaques, inflammatory lesions or tumors. Here we present an overview of radiolabelled MMP inhibitors (MMPIs) and MMP peptides for positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the detection of proteolytic activity of MMPs. So far, most studies are at a preliminary stage; however, some hydroxamate-based tracers such as the peptidomimetics [111In]-DTPA-RP782, [99mTc]-(HYNIC-RP805)(tricine)(TPPTS), or Marimastat-ArB[18F]F3 and the picolyl- benzenesulfonamide [123I]I-HO-CGS 27023A identified specifically the enzymatic action of MMPs in animal models of various pathologies. The development of new compounds that may lead to novel tracers (e.g. modification of zinc-binding group, variation of substituents attached to the S1’, S2’ and S3’ pockets of the MMP inhibitors) and the use of antibodies and cell penetrating peptides are also discussed. In general, preclinical studies with atherosclerosis models proved to be more successful than those with oncological models.

Keywords: MMP inhibitors, MMP peptides, hydroxamates, molecular imaging, PET, SPECT.

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