Novel matrix metalloproteinase inhibitor [18F]marimastat- aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer

Ulrich Auf Dem Keller, Caroline L. Bellac, Ying Li, Yuanmei Lou, Philipp F. Lange, Richard Ting, Curtis Harwig, Reinhild Kappelhoff, Shoukat Dedhar, Michael J. Adam, Thomas J. Ruth, François Bénard, David M. Perrin, Christopher M. Overall

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Matrix metalloproteinases (MMP), strongly associated 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 observed. For molecular-targeted positron emission tomography imaging of syngeneic 67NR murine mammary carcinoma in vivo, marimastat was 18F-labeled using a shelf-stable arylboronic ester conjugate as a captor for aqueous [18F]fluoride in a novel, rapid one-step reaction at ambient temperature. [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 experiments, confirming the ease of this new labeling strategy.

Original languageEnglish
JournalCancer Research
Volume70
Issue number19
Pages (from-to)7562-7569
ISSN0008-5472
DOIs
Publication statusPublished - 2010
Externally publishedYes

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