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

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 localizat...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2010-10, Vol.70 (19), p.7562-7569
Main Authors: AUF DEM KELLER, Ulrich, BELLAC, Caroline L, RUTH, Thomas J, BENARD, François, PERRIN, David M, OVERALL, Christopher M, YING LI, YUANMEI LOU, LANGE, Philipp F, RICHARD TING, HARWIG, Curtis, KAPPELHOFF, Reinhild, DEDHAR, Shoukat, ADAM, Michael J
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Borates - chemistry
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - enzymology
Cell Line, Tumor
Enzyme Inhibitors - chemistry
Female
Fluorine Radioisotopes - chemistry
Humans
Hydroxamic Acids - chemistry
Isoenzymes
Isotope Labeling - methods
Mammary Neoplasms, Experimental - diagnostic imaging
Mammary Neoplasms, Experimental - enzymology
Matrix Metalloproteinase Inhibitors
Medical sciences
Mice
Mice, Inbred BALB C
Pharmacology. Drug treatments
Positron-Emission Tomography - methods
Radiopharmaceuticals - chemical synthesis
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-10-1584