title: Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate.
abstract: Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a simpler purification method. This ultimately enhances the potential of [11C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.
authors.affiliation: Service Hospitalier Frédéric Joliot, Département de Recherche Médicale, CEA/DSV, 4 place du Général Leclerc, F-91401 Orsay, France.
authors.forename: C
authors.initials: C
authors.lastname: Thominiaux
authors.forename: F
authors.initials: F
authors.lastname: Dollé
authors.forename: M L
authors.initials: ML
authors.lastname: James
authors.forename: Y
authors.initials: Y
authors.lastname: Bramoullé
authors.forename: H
authors.initials: H
authors.lastname: Boutin
authors.forename: L
authors.initials: L
authors.lastname: Besret
authors.forename: M-C
authors.initials: MC
authors.lastname: Grégoire
authors.forename: H
authors.initials: H
authors.lastname: Valette
authors.forename: M
authors.initials: M
authors.lastname: Bottlaender
authors.forename: B
authors.initials: B
authors.lastname: Tavitian
authors.forename: Ph
authors.initials: P
authors.lastname: Hantraye
authors.forename: S
authors.initials: S
authors.lastname: Selleri
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008698:Mesylates / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D008024:Ligands; D008698:Mesylates; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; C078465:methyl triflate