Journal
JOURNAL OF ORGANOMETALLIC CHEMISTRY
Volume 791, Issue -, Pages 204-213Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jorganchem.2015.05.033
Keywords
Tetrazine; Carborane; Radioiodination; Bioorthogonal; Imaging; Targeted
Categories
Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Ontario Institute for Cancer Research (SOP-PRAR-MAC)
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Carborane-tetrazine derivatives were developed that can be used to enable boron clusters to bind specific targets in vivo using pretargeting strategies and bioorthogonal inverse electron demand DielseAlder chemistry. Specifically, 1,12-dicarba-closo-dodecaborate-1-(4-(1,2,4,5-tetrazin-3-yl) phenyl) methanamide and 1,2-dicarba-closo-dodecaborate-1-(4-(1,2,4,5-tetrazin-3-yl) phenyl) methanamide were synthesized in 49% and 78% yield respectively, and X-ray structures of both compounds determined. The ortho-carborane derivative was converted to the corresponding nido-cluster under mild conditions, and the product successfully radiolabelled with 125I and 123I. The carborane-tetrazines react rapidly and in quantitative yields with (E)-cyclooct-4-enol (TCO) via a [4 + 2] inverse-electron demand DielseAlder type reaction, where the second order rate constant in acetonitrile for the iodinated cluster was 199 +/- 26 M(-1)s(-1). The labelled tetrazines were stable in solution for extended periods and they were shown to bind in vitro to H520 cells, labelled with a TCO-modified antibody. Imaging studies on the I-123-labeled carborane-tetrazine were performed in healthy mice, and demonstrated minimal loss of iodine in vivo and high uptake in the liver and gall bladder. The reported compounds offer an alternative means of developing targeted boron neutron capture therapy (BNCT) and boron-based molecular imaging agents. (C) 2015 Published by Elsevier B.V.
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