Synthesis and radiolabeling of N-[4-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide -- a potential radiotracer for D3 receptor imaging with PET.
FAUC346 (N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), an in vitro D(3)-selective ligand, and its normethyl derivative have been synthesized from commercially available 1-(2-substituted-phenyl)piperazines. FAUC346 has been labeled using [(11)C]methyl triflate in acetone containing aqueous NaOH (5 Eq) at -10 degrees C for 1 min, purified on semipreparative reverse-phase high-performance liquid chromatography (HPLC) and formulated as an intravenous injectable solution using a Sep-Pak Plus C(18) device. Up to 5.5 GBq of [(11)C]FAUC346 (N-[4-[4-(2-[methyl-(11)C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene-2-carboxamide), with a specific radioactivity of 45-75 GBq/micromol, could be obtained in 30-35 min, including HPLC purification and formulation starting from 44.4 GBq of [(11)C]carbon dioxide. Preliminary pharmacological evaluation of [(11)C]FAUC346 in rat brain clearly demonstrated in vivo selectivity for D(3) receptors and the absence of radiolabeled metabolite within the brain. These encouraging results, however, could not be confirmed in nonhuman primates; therefore, this radioligand does not appear to have the required pharmacological profile for a positron emission tomography probe for imaging D(3) receptors.
Kuhnast
Bertrand
B
Service Hospitalier Frédéric Joliot, SHFJ/CEA/DSV, 4 place du Général Leclerc, 91401 Orsay, France.
Valette
Héric
H
Besret
Laurent
L
Demphel
Stéphane
S
Coulon
Christine
C
Ottaviani
Michèle
M
Guillermier
Martine
M
Bottlaender
Michel
M
Dollé
Frédéric
F
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D007553:Isotope Labeling; D008297:Male; D010215:Papio; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000032:analysis*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; C467222:FAUC 346; D010879:Piperazines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3; D013876:Thiophenes