Novel tetradentate diamine dioxime ligands: synthesis, characterization and in vivo behavior of their 99m Tc‐complexes

Two novel diamine dioxime ligands, 4,7‐diaza‐3,8‐diethyldecane‐2,9‐dione bis oxime (3) and 4,9‐diaza‐3,10‐diethyldodecane‐2,11‐dione bis oxime (5), were synthesized in order to develop new brain perfusion imaging agents, based on 99m Tc(V)‐complexes. The synthesis involved condensation of 2‐hydroxyi...

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Published in:Applied organometallic chemistry 2012-07, Vol.26 (7), p.347-355
Main Authors: Mirković, Marija, Janković, Drina, Vranješ‐Đurić, Sanja, Radović, Magdalena, Stanković, Dragana, Mijin, Dušan, Nikolić, Nadežda
Format: Article
Language:English
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Summary:Two novel diamine dioxime ligands, 4,7‐diaza‐3,8‐diethyldecane‐2,9‐dione bis oxime (3) and 4,9‐diaza‐3,10‐diethyldodecane‐2,11‐dione bis oxime (5), were synthesized in order to develop new brain perfusion imaging agents, based on 99m Tc(V)‐complexes. The synthesis involved condensation of 2‐hydroxyimino‐3‐pentanone with appropriate diamine in protic solvent which afforded the bis imine adducts. Subsequent reduction of imine functional groups yielded a diastereoisomeric mixture of 3 and 5. UV–visible, IR, 1 H NMR, 13 C NMR and elemental analysis were used to characterize the structures of the synthesized compounds. 99m Tc‐complexes of both diamine dioximes were prepared and radiolabeling conditions optimized to give the maximum yield. Physicochemical parameters of the labeled complexes as well as and their biodistribution in rats were investigated. Both compounds (3 and 5) formed 99m Tc‐complexes with a net charge of zero, determined by electrophoresis. The resultant lipophilic 99m Tc‐complexes of 3 and 5 were readily formed at pH ~9.0 within 10 min at room temperature with yields of 90% and 95%, respectively. The 99m Tc‐3 complex was found to be stable within 1 h, while 99m Tc‐5 was stable for a few hours. A significant brain uptake of 99m Tc‐3 (2.1% injected dose) and 99m Tc‐5 (1.8% injected dose) complexes, 2 min after injection, is in accordance with their lipophilicity. The present study suggests that both ligands are promising candidates as new 99m Tc‐based brain‐imaging agents. Copyright © 2012 John Wiley & Sons, Ltd.
ISSN:0268-2605
1099-0739
DOI:10.1002/aoc.2870