1 research outputs found
Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New <sup>18</sup>F‑Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography
New
fluorinated, arylsulfone-based matrix metalloproteinase (MMP)
inhibitors containing carboxylate as the zinc binding group were synthesized
as radiotracers for positron emission tomography. Inhibitors were
characterized by <i>K</i><sub>i</sub> for MMP-2 in the nanomolar
range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14.
Two of these compounds were obtained in the <sup>18</sup>F-radiolabeled
form, with radiochemical purity and yield suitable for preliminary
studies in mice xenografted with a human U-87 MG glioblastoma. Target
density in xenografts was assessed by Western blot, yielding <i>B</i><sub>max</sub>/<i>K</i><sub>d</sub> = 14. The
biodistribution of the tracer was dominated by liver uptake and hepatobiliary
clearance. Tumor uptake of <sup>18</sup>F-labeled MMP inhibitors was
about 30% that of [<sup>18</sup>F]Âfluorodeoxyglucose. Accumulation
of radioactivity within the tumor periphery colocalized with MMP-2
activity (evaluated by in situ zimography). However, specific tumor
uptake accounted for only 18% of total uptake. The aspecific uptake
was ascribed to the high binding affinity between the radiotracer
and serum albumin