2 research outputs found
A New Generation of Radiofluorinated Pyrimidine-2,4,6-triones as MMP-Targeted Radiotracers for Positron Emission Tomography
Radiolabeled C-5-disubstituted pyrimidine-2,4,6-triones
have recently
been suggested by our group as a class of potent matrix metalloproteinase
(MMP) targeted radiotracers that can noninvasively visualize activated
MMPs by means of positron emission tomography (PET). MMPs belong to
the zinc- and calcium-dependent endopeptidases which are involved
in the proteolytic degradation of components of the extracellular
matrix (ECM) but also are capable of processing and releasing bioactive
molecules such as growth factors, proteinase inhibitors, and cytokines.
Locally increased levels of activated MMPs modulate and contribute
to the progression of various diseases, such as cancer, atherosclerosis,
stroke, arthritis, and others. Therefore, activated MMPs are suitable
biological targets for the specific and noninvasive visualization
of aforementioned pathologies in vivo. On the basis of our recent results, we here describe a series of
new fluorinated pyrimidine-2,4,6-triones of the second generation
with maintained MMP inhibition potencies (IC<sub>50</sub> = 4–605
nM), which are fine-tuned toward more hydrophilic versions, and show
the improved biodistribution behavior of one selected radiofluorinated
pyrimidine-2,4,6-trione by means of small-animal PET