The selective dopamine D(3) receptor ligands N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]1-methoxy-2-naphthalencarboxamide (1) and N-4-[4-[(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (2) were labeled with (11)C (t(1/2) = 20.4 min) as potential radioligands for the noninvasive assessment of the dopamine D(3) neurotransmission system in vivo with positron emission tomography (PET). The radiosynthesis consisted in an O-methylation of the des-methyl precursors N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-1-hydroxy-2-naphthalenecarboxamide (3) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-hydroxy-2-benzofurancarboxamide (4) with [(11)C]methyl iodide using tBuOK/HMPA and KOH/DMSO, respectively. The radiotracers [(11)C]1 and [(11)C]2 were obtained in 35 min with over 99% radiochemical purity, 74 +/- 37 GBq/mumol of specific radioactivity, 13% and 26% radiochemical yield (EOB, decay-corrected). Distribution studies in rats demonstrated that the new tracers [(11)C]1 and [(11)C]2 cross the blood-brain barrier and localize in the brain. However, the kinetics of cerebral uptake did not reflect the regional expression of the D(3) receptors. Despite their in vitro pharmacological profile, [(11)C]1 and [(11)C]2 do not display an in vivo behavior suitable to image D(3) receptor expression using PET.
Turolla, E.A., Matarrese, M., Belloli, S., Moresco, R.M., Simonelli, P., Todde, S., et al. (2005). 11C-Labelling of N-[4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide Derivatives and Evaluation as Potential Radioligands for PET imaging of Dopamine D3 Receptors. JOURNAL OF MEDICINAL CHEMISTRY, 48(22), 7018-7023 [10.1021/jm050171k].
Citazione: | Turolla, E.A., Matarrese, M., Belloli, S., Moresco, R.M., Simonelli, P., Todde, S., et al. (2005). 11C-Labelling of N-[4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide Derivatives and Evaluation as Potential Radioligands for PET imaging of Dopamine D3 Receptors. JOURNAL OF MEDICINAL CHEMISTRY, 48(22), 7018-7023 [10.1021/jm050171k]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Titolo: | 11C-Labelling of N-[4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide Derivatives and Evaluation as Potential Radioligands for PET imaging of Dopamine D3 Receptors | |
Autori: | Turolla, EA; Matarrese, M; Belloli, S; Moresco, RM; Simonelli, P; Todde, S; Fazio, F; Magni, F; Kienle, MG; Leopoldo, M; Berardi, F; Colabufo, NA; Lacivita, E; Perrone, R | |
Autori: | ||
Data di pubblicazione: | 2005 | |
Lingua: | English | |
Rivista: | JOURNAL OF MEDICINAL CHEMISTRY | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1021/jm050171k | |
Appare nelle tipologie: | 01 - Articolo su rivista |