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 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.
auf dem Keller
Ulrich
U
UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Bellac
Caroline L
CL
Li
Ying
Y
Lou
Yuanmei
Y
Lange
Philipp F
PF
Ting
Richard
R
Harwig
Curtis
C
Kappelhoff
Reinhild
R
Dedhar
Shoukat
S
Adam
Michael J
MJ
Ruth
Thomas J
TJ
Bénard
François
F
Perrin
David M
DM
Overall
Christopher M
CM
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
D001881:Borates; D004791:Enzyme Inhibitors; D005462:Fluorine Radioisotopes; D006877:Hydroxamic Acids; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D019275:Radiopharmaceuticals; C100342:marimastat; C098759:fluoroboric acid