Title: Development and biological evaluation of 99mTc-BAT-tropane esters
Authors: Vanbilloen, Hubert P ×
Kieffer, Davy
Cleynhens, Bernard
Bormans, Guy
Mortelmans, Luc
Verbruggen, Alfons #
Issue Date: Aug-2005
Publisher: Pergamon Press
Series Title: Nuclear Medicine and Biology vol:32 issue:6 pages:607-612
Abstract: Two (99m)Tc-BAT-tropane conjugates, i.e., technetium(V)-oxo-3-[N-(2-mercaptoethyl), N-(N'-(2-mercaptoethyl)-2-aminoethyl)]-aminopropyl 3beta-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]octane-2beta-carboxylate and the corresponding norchloro derivative, were prepared and evaluated as potential imaging agents for the central nervous dopamine transporter (DAT) system. In these compounds, a tropane and a (99m)Tc-BAT moiety were linked through an ester bond. Both compounds were formed as a mixture of two diastereomers which could be purified and isolated using reversed-phase high-performance liquid chromatography (HPLC). Radio-LC-MS analysis supported the hypothesised structure of the synthesised technetium complexes. After intravenous injection in mice and rats, the compounds were stable in vivo, and no important metabolites were found in plasma or urine. In vitro testing suggested specific competitive binding to the DAT system, but in vivo experiments in rats showed no significant brain uptake for the diastereomers of both compounds; neither was there any specific uptake in the striatum. The results suggest that replacement of a methylene linker by an ester does not seriously affect the binding properties of the tropane conjugates to the dopamine transporter but results in a drastic reduction of passage over the blood-brain barrier (BBB).
ISSN: 0969-8051
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Radiopharmaceutical Research
Laboratory of Clinical Bacteriology and Mycology
Nuclear Medicine & Molecular Imaging
× corresponding author
# (joint) last author

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