Synthesisand Preliminary Evaluation in Tumor BearingMice of New 18F-Labeled Arylsulfone Matrix MetalloproteinaseInhibitors as Tracers for Positron Emission Tomography.

Newfluorinated, arylsulfone-based matrix metalloproteinase (MMP)inhibitors containing carboxylate as the zinc binding group were synthesizedas radiotracers for positron emission tomography. Inhibitors werecharacterized by Kifor MMP-2 in the nanomolarrange and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14.Two of these compounds were obtained in the 18F-radiolabeledform, with radiochemical purity and yield suitable for preliminarystudies in mice xenografted with a human U-87 MG glioblastoma. Targetdensity in xenografts was assessed by Western blot, yielding Bmax/Kd= 14. Thebiodistribution of the tracer was dominated by liver uptake and hepatobiliaryclearance. Tumor uptake of 18F-labeled MMP inhibitors wasabout 30% that of [18F]fluorodeoxyglucose. Accumulationof radioactivity within the tumor periphery colocalized with MMP-2activity (evaluated by in situ zimography). However, specific tumoruptake accounted for only 18% of total uptake. The aspecific uptakewas ascribed to the high binding affinity between the radiotracerand serum albumin. [ABSTRACT FROM AUTHOR]