Pharmacological characterization and positron emission tomography evaluation of 4-[ 76Br]bromodexetimide and 4-[ 76Br]bromolevetimide for investigations of central muscarinic cholinergic receptors

• Published in: Nuclear medicine and biology Vol. 23; no. 3; pp. 235 - 243
• Main Authors: Loc'h, C., Kassiou, M., Strijckmans, V., Bottlaender, M., Katsifis, A., Schmid, L., Mazière, M., Lambrecht, R.M., Mazière, B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.1996; Elsevier
• Subjects: Animals; Autoradiography; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Bromine Radioisotopes - pharmacokinetics; Bromine-76; Cell Membrane - metabolism; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Contrast media. Radiopharmaceuticals; Dexetimide; Dexetimide - analogs & derivatives; Dexetimide - chemical synthesis; Dexetimide - pharmacokinetics; Frontal Lobe - metabolism; Isotope Labeling - methods; Kinetics; Levetimide; Male; Medical sciences; Muscarinic Antagonists; Muscarinic cholinergic receptors; Pharmacology. Drug treatments; Positron Emission Tomography; Radioligand Assay; Radiotracers; Rats; Rats, Wistar; Receptors, Muscarinic - analysis; Receptors, Muscarinic - metabolism; Tissue Distribution; Tomography, Emission-Computed - methods; Levetimide; Radiotracers; Dexetimide; Bromine-76; Muscarinic cholinergic receptors; Positron Emission Tomography; Radionuclide study; Bromine; Radiolabelling; Rat; Rodentia; In vitro; Vertebrata; Mammalia; Animal; Radiochemistry; Pharmacokinetics; Chemical synthesis; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/0969-8051(95)02052-7

4-[ 76Br]bromodexetimide and its inactive enantiomer 4-[ 76Br]bromolevetimide were prepared via electrophilic bromodesilylation using chloramine-T and no-carrier-added (NCA) [ 76Br]NH 4. In vitro, B max measured on rat cortex membranes were 3.7 ± 0.2 and <0.07 pmol/mg protein for 4-[ 76Br]bromodexetimide and 4-[ 76Br]bromolevetimide, respectively. The k D of 4-[ 76Br]bromodexetimide was 1.9 ± 0.3 nM. In vivo studies in rats showed specific uptake of 4-[ 76Br]bromodexetimide in cortex, striatum, thalamus and hippocampus. No specific uptake was observed with 4-[ 76Br]bromolevetimide. With [ 76Br]bromodexetimide, positron emission tomography (PET) studies in primates demonstrated a preferential accumulation of the radioactivity in the cortex and striatum which was displaced to the level of cerebellum by dexetimide. With 4-[ 76Br]bromolevetimide, the radioactivity concentrations in the cortex and striatum were similar to that of cerebellum.