title: Novel matrix metalloproteinase inhibitor [18F]marimastat-aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer.
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 (18)F-labeled using a shelf-stable arylboronic ester conjugate as a captor for aqueous [(18)F]fluoride in a novel, rapid one-step reaction at ambient temperature. [(18)F]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.
authors: UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Ulrich
authors: U
authors: auf dem Keller
authors: Caroline L
authors: CL
authors: Bellac
authors: Ying
authors: Y
authors: Li
authors: Yuanmei
authors: Y
authors: Lou
authors: Philipp F
authors: PF
authors: Lange
authors: Richard
authors: R
authors: Ting
authors: Curtis
authors: C
authors: Harwig
authors: Reinhild
authors: R
authors: Kappelhoff
authors: Shoukat
authors: S
authors: Dedhar
authors: Michael J
authors: MJ
authors: Adam
authors: Thomas J
authors: TJ
authors: Ruth
authors: François
authors: F
authors: Bénard
authors: David M
authors: DM
authors: Perrin
authors: Christopher M
authors: CM
authors: Overall
mesh_terms: D000818:Animals; D001881:Borates / Q000737:chemistry; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D007527:Isoenzymes; D007553:Isotope Labeling / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000201:enzymology; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis
chemical_list: D001881:Borates; D004791:Enzyme Inhibitors; D005462:Fluorine Radioisotopes; D006877:Hydroxamic Acids; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D019275:Radiopharmaceuticals; C100342:marimastat; C098759:fluoroboric acid