During the past few years, several imaging probes targeting
matrix metalloproteinases (
MMPs) have been developed. Most of these probes have been validated in animal models. Overall, results derived from most of these studies have been disappointing. Whether or not this relates to shortcomings of the imaging probes used or to the set-up of the reported studies is currently unclear. Firstly,
MMPs targeted in these studies, MMP-1, -2 and -9, are cell secreted and their expression is known to vary extensively within one
tumor type, depending on the stage of development of the
tumor and on the presence of naturally occurring TIMPs. Given the lack of data on the levels of
MMP expression by incoculated
tumor tissue at the time of imaging in most studies reported, it cannot be excluded that the negative results reported are, in fact, false-negative imaging results. Secondly, given that most of the agents used for imaging are intrinsically broad-spectrum agents, their higher affinity for specific subsets of
MMPs does not necessarily imply that a positive imaging result also corresponds to overexpression of specific subsets of
MMPs, as suggested in some papers published. Accordingly, well-characterized
tumor models need to be developed for the purpose of validating currently available, as well as future,
MMP-imaging probes. So far, only
111In-DTPA-N-TIMP-2 has been injected in patients, respectively suffering from
Kaposi Sarcoma. Imaging results obtained with this agent proved disappointing. Imaging results obtained with other
MMP-targeting probes in patients are awaited.