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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