Synthesis of two potential NK1-receptor ligands using 1-11Cethyl iodide and 1-11Cpropyl iodide and initial PET-imagingReportar como inadecuado

Synthesis of two potential NK1-receptor ligands using 1-11Cethyl iodide and 1-11Cpropyl iodide and initial PET-imaging - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Imaging

, 7:6

First Online: 30 July 2007Received: 19 March 2007Accepted: 30 July 2007


BackgroundThe previously validated NK1-receptor ligand O-methyl-CGR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on O-methyl-CGR205171.

Methods1-CEthyl and 1-Cpropyl iodide with specific radioactivities of 90 GBq-μmol and 270 GBq-μmol, respectively, were used in the synthesis of O-methyl-CGR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained 2S,3S-N-1-2- 1-Cethoxy-5-3-trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine I and 2S,3S-2-phenyl-N-1-2- 1-Cpropoxy-5-3-trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of O-methyl-CGR205171.

ResultsAll ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that II had no specific binding in striatum. Ligand I had moderate specific binding compared to the O-methyl-CGR205171. The ethyl analogue I displayed reversible binding characteristics contrary to the slow dissociation rate shown by O-methyl-CGR205171.

ConclusionThe propyl-analogue II cannot be used for detecting changes in NK1-ligand levels, while further studies should be performed with the ethyl-analogue I .

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2342-7-6 contains supplementary material, which is available to authorized users.

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Autor: Stina Syvänen - Jonas Eriksson - Tove Genchel - Örjan Lindhe - Gunnar Antoni - Bengt Långström


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