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Synthesis, radio‐LC‐MS analysis and biological evaluation of 99m Tc‐techmazenil
Author(s) -
Kieffer Davy,
Cleynhens Bernard,
Verbeke Kristin,
Vanbilloen Hubert,
de Groot Tjibbe,
Terwinghe Christelle,
Verbruggen Alfons,
Bormans Guy
Publication year - 2004
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.813
Subject(s) - chemistry , flumazenil , biodistribution , clearance , metabolite , high performance liquid chromatography , ligand (biochemistry) , in vitro , receptor , benzodiazepine , chromatography , pharmacology , stereochemistry , biochemistry , medicine , urology
A 99m Tc‐labelled compound with the biological characteristics of flumazenil would be useful for determination of neuronal viability after the onset of a stroke. Therefore, we have derivatized Ro‐15‐3890 (a flumazenil metabolite bearing a carboxylic acid group instead of an ethyl ester) by coupling it with a bisamino bisthiol tetraligand bearing a 3‐hydroxypropyl side chain (3‐hydroxypropyl‐BAT) to enable labelling with technetium‐99m. After purification by RP‐HPLC, the ligand was deprotected and labelled in a ‘one pot’ reaction, yielding a 99m Tc‐BAT‐propylester of Ro‐15‐3890 ( 99m Tc‐techmazenil). Radio‐LC‐MS analysis of the isolated main peak showed the molecular ion mass (608.0618) of the expected 99m Tc‐techmazenil. The biodistribution of 99m Tc‐techmazenil was investigated in normal mice and indicated that the tracer is cleared from plasma mainly by the hepatobiliary system and shows a very low uptake in brain. In vitro binding studies on mice brain slices indicated that techmazenil does not bind to benzodiazepine receptors. Copyright © 2004 John Wiley & Sons, Ltd.