Synthesis, radio‐LC‐MS analysis and biological evaluation of ^99mTc‐techmazenil

Abstract

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 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.

Synthesis and biological evaluation of a technetium-99m(I)-tricarbonyl-labelled phenyltropane derivative

“…Analysis of the assumed isomers by paper electrophoresis ( Log P oct/buffer values were determined using a published procedure 22 and found to be 2.14 ± 0.02 for isomer A and 2.12 ± 0.03 for isomer B, both compatible with reasonable brain uptake. Indeed, an optimal passage over the BBB is suggested for compounds with log P oct/buffer values ranging from 1 to 2.5.…”

27 Radiochemistry and radiopharmaceuticals

“…The chelation of technetium by ligands based on two nitrogen and two sulfur atoms ('N2S2') has been used to label both techmazenil 137 and a thymidine 138 analogues whilst an N3S ligand was used to produce 139 the technetium-labelled a-M2 peptide A series of nitroimidazole complexes [140][141][142] has been used for tumour imaging in mice. Other recently reported complexes of technetium that have been used in nuclear medicine include [ 99m Tc]-IOIDA (3-iodo-2,4,6-trimethylphenyl carbamoylmethyl iminodiacetic acid), 143 [ 99m Tc]-DMS (dimercaptosuccinic acid), 144 a series of aminophosphonate 145 complexes, technetium 2,3-dimethyl-cyclo-hexylisonitrile, 146 and complexes of biotin, 147 octreotide 148 and estrogen.…”

“…An extensive adsorption-diffusion study [231][232][233] has been made of tritiated water, sodium, caesium and iodide ions on opalinus clay and also of the ability of various polymers and resins to adsorb cobalt-60, 234 thorium, 235 uranium, 235 plutonium and americium 236 from aqueous solutions and from sludge. 237 Cobalt-60 can also be adsorbed 238 by manganese(IV) oxide, 137 Cs and 90 Sr by silica gel 239 and promethium by rutile and goethite. 240 Quartz sand has been shown to be effective in the adsorption of thorium, 241 and this element, together with uranium (as UO 2 2+ ) can be adsorbed by cellulose.…”