Journal of labelled compounds & radiopharmaceuticals vol:47 issue:3 pages:199-208
A Tc-99m-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 Tc-99m-BAT-propylester of Ro-15-3890 (Tc-99m-techmazenil). Radio-LC-MS analysis of the isolated main peak showed the molecular ion mass (608.0618) of the expected Tc-99m-techmazenil. The biodistribution of Tc-99m-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 (C) 2004 John Wiley Sons, Ltd.