Novel Matrix Metalloproteinase Inhibitor [18F]Marimastat-Aryltrifluoroborate as a Probe for In vivo Positron Emission Tomography Imaging in Cancer.

Matrix metalloproteinases (MMP), strongly assocd. pathogenic markers of cancer, have undergone extensive drug development programs. Marimastat, a noncovalent MMP inhibitor, was conjugated with FITC to label cellular metalloproteinase cancer targets in MDA-MB-231 cells in vitro. Punctate localization of active transmembrane MMP14 was obsd. For mol.-targeted positron emission tomog. imaging of syngeneic 67NR murine mammary carcinoma in vivo, marimastat was 18F-labeled using a shelf-stable arylboronic ester conjugate as a captor for aq. [18F]fluoride in a novel, rapid one-step reaction at ambient temp. [18F]Marimastat-aryltrifluoroborate localized to the tumors, with labeling being blocked in control animals first loaded with >10-fold excess unlabeled marimastat. The labeled drug cleared primarily via the hepatobiliary and gastrointestinal tract, with multiple animals imaged in independent expts., confirming the ease of this new labeling strategy. Cancer Res; 70(19); 7562-9. [on SciFinder(R)]